Lolcat and Valproate: Difference between pages

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{{drugbox |
<!-- See talk page for discussion on this image; please do not change without consensus -->
| IUPAC_name = 2-propylpentanoic acid
A '''lolcat''' is an image combining a [[photograph]], most frequently a [[cat]], with a [[humorous]] and [[Idiosyncrasy|idiosyncratic]] [[caption]] in (often) broken [[English language|English]]—a dialect which is known as "lolspeak", or "kitteh". The name "lolcat" is a [[Compound (linguistics)|compound word]]<!-- note: not a portmanteau --> of "[[LOL]]" and "cat".<ref name="Silverman">{{cite web
| image = Valproic-acid-2D-skeletal.png
| author = Dwight Silverman
| width=180
| title = Web photo phenomenon centers on felines, poor spelling
| CAS_number = 99-66-1
| publisher = [[Houston Chronicle]]
| ATC_prefix = N03
| date = 2007-06-06
| ATC_suffix = AG01
| url = http://www.chron.com/disp/story.mpl/business/4862013.html
| PubChem = 3121
| accessdate = 2008-09-21 }}
| DrugBank = APRD00256
</ref> Another name is '''cat macro''', being a type of [[image macro]].<ref name="beacon">{{cite news
| C=8 | H=16 | O=2
| url = <!--http://www.ohio.com/mld/beaconjournal/living/17346291.htm-->
| smiles = CCCC(CCC)C(=O)O
| title = Laugh at cat humor
| molecular_weight = 144.211 g/mol
| author = Randy A. Salas
| bioavailability = Rapid absorption
| work = [[Akron Beacon Journal]], [[Star Tribune]]
| protein_bound = Concentration-dependent, from 90% at 40&nbsp;µg/mL to 81.5% at 130&nbsp;µg/mL
| date = [[2007-06-09]]
| metabolism = [[Liver|Hepatic]]—[[glucuronidation|glucuronide conjugation]] 30–50%, mitochondrial β-oxidation over 40%
| accessdate = 2007-06-17
| elimination_half-life = 9–16 hours
| quote = At first, they were called cat macros, but now go mostly by the name lolcats.
| excretion = Less than 3% excreted unchanged in urine.
}}</ref> Lolcats are created for [[photo sharing]] [[imageboard]]s and other internet forums. Lolcats are similar to other [[anthropomorphism|anthropomorphic]] animal-based image macros such as the [[O RLY?]] owl.<ref name="slate">{{cite news
| licence_US = Valproic+acid
| last = Agger
| pregnancy_category = D—[[teratogenic]]
| first = Michael
| legal_US = Rx-only
| title = Cat power: You cannot resist lolcats
| legal_UK = POM
| work = [[Slate (magazine)|Slate Magazine]]
| routes_of_administration = Oral, [[intravenous therapy|intravenous]]
| date = [[2007-05-21]]
}}
| url = http://www.slate.com/id/2166338/
'''Valproic acid''' ('''VPA''') is a [[chemical compound]] that has found clinical use as an [[anticonvulsant]] and [[mood stabilizer|mood-stabilizing]] [[medication|drug]], primarily in the treatment of [[epilepsy]], [[bipolar disorder]], and less commonly [[major depressive disorder|major depression]]. It is also used to treat [[migraine headache|migraine]] [[headache]]s and [[schizophrenia]].
| accessdate = 2007-05-21
}}</ref>


Related drugs include the sodium salts [[sodium valproate]], used as an anticonvulsant, and a combined formulation, [[valproate semisodium]], used as a mood stabilizer and additionally in the U.S. also as an anticonvulsant.
The term ''lolcat'' gained national media attention in the [[United States]] when it was covered by [[Time (magazine)|''Time'']],<ref name="Time">{{cite news
|first=Lev |last=Grossman
| url = http://www.time.com/time/magazine/article/0,9171,1642897,00.html
| title = Cashing in on Cute Cats
| authorlink = Lev Grossman
| date = [[2007-07-12]]
| accessdate 2007-07-12
| work = [[Time Magazine]]
}} Partial scan of the print edition: http://fcrunk.wellimean.com/memes/catstime.jpg</ref> which wrote that non-commercialized [[phenomenon|phenomena]] of the sort are increasingly rare, stating that lolcats have "a distinctly old-school, early 1990s, [[Usenet]] feel to [them]." The superimposed text is usually assumed to be uttered by the cat in the photograph. There are parallels between the language used in lolcats and [[baby talk]], which some owners of cats often use when talking to them.{{Fact|date=September 2008}}


== Format ==
==History==
Valproic acid (by its official name ''2-propylvaleric acid'') was first synthesized in 1882 by Burton as an [[analog (chemistry)|analogue]] of [[valeric acid]], found naturally in [[Valerian (herb)|valerian]].<ref>Burton BS (1882). On the propyl derivatives and decomposition products of ethylacetoacetate. ''Am Chem J.'' 3:385-395.</ref> A clear liquid fatty acid at room temperature, for many decades its only use was in laboratories as a "metabolically inert" solvent for organic compounds. In 1962, the French researcher Pierre Eymard serendipitously discovered the anticonvulsant properties of valproic acid while using it as a vehicle for a number of other compounds that were being screened for anti-seizure activity. He found that it prevented [[pentylenetetrazol]]-induced convulsions in rodents.<ref>Meunier H, Carraz G, Meunier Y, Eymard P, Aimard M. (1963). Propriétés pharmacodynamiques de l’acide n-dipropylacetique. ''Therapie'' 18:435-438.</ref> Since then it has also been used for migraine and bipolar disorder.<ref>Henry T.R. (2003). The History of Valproate in Clinical Neuroscience. ''Psychopharmacology bulletin'' 37 (Suppl 2):5-16</ref>
These images usually consist of a photo of a cat with a large caption characteristically set in a [[sans serif]] font such as [[Impact (typeface)|Impact]] or [[Arial Black]].<!--<ref name="cats has grammar">{{cite web|url=http://www.dashes.com/anil/2007/04/cats-can-has-gr.html|title=Anil Dash: Cats Can Has Grammar|author=[[Anil Dash]]|date=[[2007-04-23]]|accessdate=2007-05-03}}</ref>--> The image is, on occasion, [[Photo editing|digitally edited]] for effect. The caption generally acts as a [[speech balloon]] encompassing a comment from the cat, or as a description of the depicted scene. The caption is intentionally written with deviations from standard English spelling and syntax,{{Fact|date=September 2008}}<!--<ref name= "cats has grammar" />--> featuring "strangely-conjugated verbs, but a tendency to converge to a new set of rules in spelling and grammar."<ref name="Newitz 2007">{{cite web
| url = http://blog.wired.com/tableofmalcontents/2007/04/im_in_yr_x_ying.html
| title = I'M IN YR X Y-ING YOUR Z -- A Grammar of Lolcats
| author = [[Annalee Newitz]]
| publisher = Table of Malcontents, a ''[[Wired (magazine)|Wired]]'' blog
| date = [[2007-04-27]]
| accessdate = 2007-04-29
| quote = These images... usually include a cute cat saying something related to buckets, cheeseburgers, or whatever else with strangely-conjugated verbs.
}}</ref>{{Fact|date=October 2008}}<!--<ref name= "cats has grammar" /><ref name="kitty pidgin">{{cite web
| url=http://itre.cis.upenn.edu/~myl/languagelog/archives/004442.html
| title=Language Log: Kitty Pidgin and asymmetrical tail-wags
| author=[[Mark Liberman]]|date=[[2007-04-25]]|accessdate=2007-04-28
}}</ref>--> [[Image:Wikipedia-lolcat.jpg|thumb|left|175px|A lolcat image using the "I'm in ur..." format.]]The text parodies the grammar-poor [[patois]] stereotypically attributed to [[Internet slang]]. Frequently, lolcat captions take the form of [[phrasal template]]s.<!--<ref name="kitty pidgin" />--> Some phrases have a known source (usually a well-known [[Internet meme]], such as [[All your base are belong to us]] or [[Do not want]]), while others seem to be specific to the lolcat form.{{or|date=October 2008}}


==Indications==
Common themes include jokes of the form "Im in ur ''noun'', ''verb''-ing ur ''related noun''."<ref name="tampa">{{cite news
As an anticonvulsant, valproic acid is used to control [[absence seizure]]s, [[tonic-clonic seizure]]s ([[grand mal]]), [[complex partial seizure]]s, [[juvenile myoclonic epilepsy]] and the [[seizure]]s associated with [[Lennox-Gastaut syndrome]]. It is also used in treatment of [[myoclonus]]. In some countries, [[parenteral]] (administered [[intravenous]]ly) preparations of valproate are used also as second-line treatment of [[status epilepticus]], as an alternative to [[phenytoin]]. Valproate is one of the most common drugs used to treat [[post-traumatic epilepsy]].<ref name=PosnerLorenzo>Posner E, Lorenzo N (October 11, 2006). "[http://www.emedicine.com/NEURO/topic318.htm Posttraumatic epilepsy]". Emedicine.com. Retrieved on [[2008-07-30]].</ref>
|title= This be funny storyz
|work=[[Tampa Bay Times]]
|author=Jay Cridlin
|date=2007-06-01
|url=http://www.tbt.com/entertainment/news/article41041.ece?lol
}}</ref> This construction is a [[snowclone]] stemming from the phrase "I'm in ur base, killing ur doodz," which became a common [[internet meme|meme]] in several [[real-time strategy]] [[computer game]]s. "''subject''s: i has dem" show the cat in possession of multiple, identical objects, whereas "I has a ''noun''" pictures show a cat in possession of an object. "Invisible ''noun''" show pictures of cats apparently interacting with said invisible object.<ref name="tampa" /> The related "flavor" (spelled "flavr" or "flavur" in lolcat) shots specifically show a cat (or another animal) licking/eating an item, person or animal (including sometimes themselves) and remarking how "[noun] haz a flavr." "My ''noun'', let me show you it/them" pictures are accompanied by cats apparently presenting or offering an object. Another common lolcat displays a cat with a specific look, which is described by ''adjective'', and the text, "[adjective] cat is [adjective]", "[adjective] cat is not [adjective]" or "Your offering pleases [adjective] cat." A version of this is also stated as "''adjective'' cat is not amused", or "[adjective] cat has run out of [adjective]."
<!--This paragraph does not have sources and will be considered original research unless verifiable third-party citations can be given. The only source currently given for this section is for FAIL, and that source does not confirm that there is any causal relationship between "fail" and Lolcats.
There are several well-known lolcat images and single-word captions that have spawned many variations and imitations, including "Ceiling Cat" and "Basement Cat" (or occasionally "Floor Cat") which have become the lolcat metaphors of God and Satan, respectively. Others include "I can has Cheezburger," "[[monorail]] cat," "I [''verb'']ed you a [''noun''], but I eated it", "hover cat", "Oh Hai I upgraded your [[Random-access memory|RAM]]," [[Do not want|"WANT", "DO NOT WANT!"]], "Fail",<ref>[http://technology.timesonline.co.uk/tol/news/tech_and_web/the_web/article3304328.ece Microtrends: Failure - Times Online]</ref> "Nom Nom Nom" (an [[Onomatopoeia|onomatopoeic]] word for eating), "Halp!" ("Help!), "Invisible [object or action]", "Proceed," and "Pew pew pew" (an onomatopoeic for shooting).-->


According to [[Medical News Today]], valproic acid can be used for the treatment of [[manic episodes]] associated with [[bipolar disorder]], adjunctive therapy in multiple seizure types (including epilepsy), and prophylaxis of migraine headaches<ref> {{cite news
== History ==
| last =
[[Image:Yet another lolcat.jpg|thumb|right|200px|A Lolcat image depicting a cat in an [[iMac]]]]
| first =
Many of the first lolcats originated from the anonymous [[imageboard]] [[4chan]] sometime around 2005.<ref>{{cite web | url=http://www.thestar.com/living/article/257955 | publisher=[http://www.thestar.com/ The Star] | title=Funny how `stupid' site is addictive | last=Langton | first=Jerry | date=2007-09-22 | accessdate=2008-10-04}}</ref><ref>{{cite web
| coauthors =
| url = http://media.www.dailypennsylvanian.com/media/storage/paper882/news/2007/11/14/News/Iz.Not.Cats.Everywhere.Online.Trend.Spreads.Across.Campus-3099929.shtml
| title = FDA Issues Approvable Letter For Stavzor Delayed Release Valproic Acid Capsules
| title = Iz not cats everywhere? Online trend spreads across campus}}</ref><ref>{{cite news |first=david |last=smith |title=the unseen face behind today’s counterculture |url=http://www.taipeitimes.com/News/editorials/archives/2008/07/23/2003418192 |accessdate=2008-08-25 }}</ref> The word "lolcat" is attested as early as June 2006, and the domain name "lolcats.com" was registered on June 14, 2006.<ref>[http://www.networksolutions.com/whois/results.jsp?domain=lolcats.com WHOIS domain registration information results for lolcats.com from Network Solutions<!-- Bot generated title -->]</ref> ''[[The News Journal]]'' states that "some trace the lolcats back to the site [[4chan]], which features bizarre cat pictures on Saturdays, or 'Caturdays'." Ikenburg adds that the images have been "slinking around the Internet for years under various labels, but they didn't become a sensation until early 2007 with the advent of [[I Can Has Cheezburger?]]"<ref>"Lolcats' demented captions create a new Web language", Tamara Ikenberg, ''[[The News Journal]]'', [[9 July]] [[2007]]</ref> The first image on "I CAN HAS CHEEZBURGER?" was posted on [[January 11]], [[2007]] and was allegedly from the [[Something Awful]] website."<ref>[http://icanhascheezburger.com/about About « Lolcats ‘n’ Funny Pictures - I Can Has Cheezburger?<!-- Bot generated title -->]</ref><ref>"Original Picture, cheezburger, ''ICANHASCHEEZBURGER'', [[26 September]] [[2007]] http://icanhascheezburger.com/2007/01/11/i-can-has-cheezburger/</ref> Lev Grossman of ''Time'' wrote that the oldest known example "probably dates to 2006",<ref>{{cite web
| publisher = 2007 MediLexicon International Ltd
| url = http://www.time.com/time/magazine/article/0,9171,1642897,00.htmlthis has also spawned the digg dog which is part of the popular site titled digg.com
| date = 2007-10-25
| title = Creating a Cute Cat Frenzy
| url = http://www.medicalnewstoday.com/articles/86674.php
| author = Lev Grossman
| accessdate = 2007-10-29 }} </ref>.
| publisher = [[Time (magazine)]]
It is more recently being used to treat neuropathic pain, as a second line agent, particularly lancinating pain from A* fibres.
| date = [[2007-07-12]]
===Investigational===
| accessdate = 2007-07-16
HDAC1 is needed for [[HIV]] to remain in infected cells. A study published in August 2005 found that three of four patients treated with valproic acid in addition to [[highly active antiretroviral therapy]] (HAART) showed a mean 75% reduction in latent HIV infection.<ref>{{cite journal | author = Lehrman G, Hogue I, Palmer S, Jennings C, Spina C, Wiegand A, Landay A, Coombs R, Richman D, Mellors J, Coffin J, Bosch R, Margolis D | title = Depletion of latent HIV-1 infection in vivo: a proof-of-concept study | journal = [[The Lancet|Lancet]] | volume = 366 | issue = 9485 | pages = 549–55 | year = 2005| pmid = 16099290 | doi = 10.1016/S0140-6736(05)67098-5}}</ref> Subsequent trials, however, have found no long term benefits of valproic acid in HIV infection.<ref>{{cite journal | author = Sagot-Lerolle N, Lamine A, Chaix ML, Boufassa F, Aboulker JP, Costagliola D, Goujard C, Paller C, Delfraissy JF, Lambotte O; ANRS EP39 study | title = Prolonged valproic acid treatment does not reduce the size of latent HIV reservoir | journal = [[AIDS (journal)|AIDS]] | volume = 22 | issue = 10 | pages = 1125-29 | year = 2008| pmid = 18525257}}</ref>
}}</ref> but later corrected himself in a blog post<ref>{{cite web
| url = http://time-blog.com/nerd_world/2007/07/16/
| title = Lolcats Addendum: Where I Got the Story Wrong
| author = Lev Grossman
| publisher = [[Time (magazine)]]
| date = [[2007-07-16]]
| accessdate = 2007-07-17
}}</ref> where he recapitulated the anecdotal evidence readers had sent him, placing the origin of "Caturday" and many of the images now known by a few as "lolcats" in early 2005. The domain name "caturday.com" was registered on [[April 30]], [[2005]].


According to the U.S. National Institutes of Health and others, valproic acid appears to have wide implications in the treatment of various [[cancer]]s,<ref>{{cite journal | author = Isenberg JS, Jia Y, Field L, Ridnour LA, Sparatore A, Del Soldato P, Sowers AL, Yeh GC, Moody TW, Wink DA, Ramchandran R, Roberts DD | title = Modulation of angiogenesis by dithiolethione-modified NSAIDs and valproic acid. | journal = [[Br J Pharmacol.|British Journal of Pharmacology]] | volume = Mar 12 | issue = | pages = | year = 2007 | pmid = 17273758}}</ref> including [[multiple myeloma]] (bone marrow cancer),<ref>{{cite journal | author = Schwartz C, Palissot V, Aouali N, Wack S, Brons NH, Leners B, Bosseler M, Berchem G | title = Valproic acid induces non-apoptotic cell death mechanisms in multiple myeloma cell lines. | journal = [[Int J Oncol.|International Journal of Oncology]] | volume = Mar | issue = 30 | pages = 573–82 | year = 2007 | pmid = 17273758}}</ref> [[glioma]] (an aggressive type of [[brain tumor]]),<ref>{{cite journal | author = A.M. Admirant, J. A. Hendricks, P.C. De Witt Hamer, S. Leenstra, W.P. Vandertop, C.J.F. van Noorden, and J.P. Medema | title = Valproic Acid is toxic to malignant glioma cells and increases sensitivity to irradiation and chemotherapy | journal = [[Abstracts for the Seventh Congress of the European Association for Neuro-Oncology (EANO)]] | volume = Sept 14-17 | issue = | pages = 334 | year = 2006 | id = | doi = 10.1186/1476-4598-5-71, | doi_brokendate = 2008-06-25 }}</ref> and melanoma.<ref>{{cite journal | author = Valentini A, Gravina P, Federici G, Bernardini S. | title = Valproic Acid Induces Apoptosis, p(16INK4A) Upregulation and Sensitization to Chemotherapy in Human Melanoma Cells | journal = [[Cancer Biol Ther.| Cancer Biology & Therapy]] | volume = Feb 5 | issue = 6 | pages = | year = 2007 | pmid = 17218782}}</ref> Valproic acid is cytotoxic to many different cancer types through its action as a histone-deacetylase inhibitor.
== Offshoots and parodies ==
* The [http://www.lolcatbible.com/ LOLCat Bible Translation Project] is attempting to translate the [[Bible]] into lolcat speak.<ref name="seattlepi">{{cite news | first=Monika | last=Guzman | coauthors= | title=Time Killer: The "lolcat" bible | date=[[2007-10-19]] | publisher= | url =http://blog.seattlepi.nwsource.com/thebigblog/archives/124063.asp?from=blog_last3 | work =Seattle Post-Intelligencer | pages = | accessdate = 2007-12-23 | language = }}</ref><ref name="latimes">{{cite news | first=Charlie | last=Amter | coauthors= | title=Lolcat Bible Translation Project presents the Gospel according to Fluffy | date=[[2007-12-16]] | publisher= | url =http://www.latimes.com/technology/la-ca-lolcat16dec16,1,6069575.story?ctrack=1&cset=true | work =Los Angeles Times | pages = | accessdate = 2007-12-23 | language = }}</ref><ref>[http://www.latimes.com/technology/la-ca-lolcat16dec16,1,6069575.story It's the Gospel according to kittah - Los Angeles Times<!-- Bot generated title -->]</ref><!--<ref>[http://www.modbee.com/2219/story/169247.html The Modesto Bee | The Gospel according to kitty Bot generated title ]</ref>-->
*The syntax of lolcat captions was used as the basis for [[LOLCODE]], an [[esoteric programming language]] with interpreters and compilers available in [[.NET framework]], [[perl]], etc.<ref name="Silverman"/>
<!--This entry may not be notable or desirable, and currently there are no good refs for it:
* A related phenomenon uses photos of an [[Southern Elephant Seal|elephant seal]] ("[[lolrus]]") on the search for a blue bucket ("bukkit").-->
<!--This section needs improved in-line citations.


Another potential indication may be [[leukemia]] in juvenile patients. Studies conducted by several European centres are ongoing. Although it is too early to make a definitive statement, preliminary results are encouraging.{{Fact|date=March 2007}}
=== Ceiling cat ===
"Ceiling Cat" is a character spawned by the Lolcat meme. The original image was a Lolcat [[image macro]] with a picture of a cat looking out of a hole in a ceiling, captioned "Ceiling Cat is watching you [[masturbate]]." There followed numerous image macros with the format "Ceiling Cat is watching you [''verb'' ending in/rhyming with -ate]" with Ceiling Cat superimposed in the upper left hand corner of an image macro depicting the appropriate action. He has subsequently evolved into a [[metaphor]] for God, particularly the God of Cats. In the [[LOLCat Bible Translation Project]], [[God]] is portrayed in the LOLCat bible and in [[lolspeak]] in general by Ceiling Cat (along with [[Satan]], who is represented by "Basement Cat", a [[black cat]] who lives in the basement).<ref name="latimes" /><ref>{{cite web|url=http://www.pittsburghlive.com/x/pittsburghtrib/news/today/s_568828.html|title=How one hungry 'kitteh' can has the Internet lol|last=Horan|first=Brianna|accessdate=2008-06-18}}</ref><ref>{{cite web|url=http://blog.seattlepi.nwsource.com/thebigblog/archives/124063.asp?from=blog_last3|title=Time killer: The "lolcat" Bible|last=Guzman|first=Monica|accessdate=2008-06-18}}</ref>
-->


==Contraindications==
== See also ==
Valproate is relatively [[contraindication|contraindicated]] in pregnancy due to its [[teratogenesis|teratogenicity]]; women who become pregnant while taking valproate should be counselled as to its risks, take high dose [[folic acid]] and be offered [[antenatal screening]] ([[alpha-fetoprotein]] and second [[trimester]] [[ultrasound scan]]s).<ref name="BNF">[[British National Formulary]] (March 2003) '''45'''</ref> It is a known folate antagonist, which can cause [[neural tube defects]]. Thus, folic acid supplements may alleviate the teratogenic problems. A recent study showed that children of mothers taking valproate during pregnancy are at risk for significantly lower IQs.<ref>{{cite web | url = http://www.medscape.com/viewarticle/549073 | title = NEAD: In Utero Exposure To Valproate Linked to Poor Cognitive Outcomes in Kids | last = Cassels | first = Caroline | date = [[December 8]] [[2006]] | publisher = Medscape | accessdate = 2007-05-23}}</ref><ref>{{cite journal |author=Meador KJ, Baker GA, Finnell RH, ''et al'' |title=In utero antiepileptic drug exposure: fetal death and malformations |journal=Neurology |volume=67 |issue=3 |pages=407–12 |year=2006 |pmid=16894099 |doi=10.1212/01.wnl.0000227919.81208.b2}}</ref> Exposure of the human [[embryo]] to valproic acid is also associated with risk of [[autism]], and it is possible to duplicate features characteristic of autism by exposing rat embryos to valproic acid at the time of neural tube closure.<ref name=Arndt>{{cite journal|journal=Int J Dev Neurosci|date=2005|volume=23|issue=2–3|pages=189–99|title=The teratology of autism|author=Arndt TL, Stodgell CJ, Rodier PM|doi=10.1016/j.ijdevneu.2004.11.001|pmid=15749245}}</ref> One study found that valproate exposure on embryonic day 11.5 led to significant local recurrent connectivity in the juvenile rat [[neocortex]], consistent with the underconnectivity theory of autism.<ref>{{cite journal|journal=Cereb Cortex|date=2007|title=Hyperconnectivity of local neocortical microcircuitry induced by prenatal exposure to valproic acid|author=Rinaldi T, Silberberg G, Markram H|doi=10.1093/cercor/bhm117|pmid=17638926 | volume = 18 | pages = 763}}</ref>
{{Commonscat|Lolcats}}
{{Spoken Wikipedia|Lolcat.ogg|2008-04-04}}
* [[List of Internet phenomena]]
* [[LOLCODE]]
* [[O RLY?]]
* [[Internet Meme]]
* [[Padonki]], a Russian Internet subculture with slang similar in format to Lolspeak


Valproate is contraindicated in overweight patients because it might cause weight gain.{{Fact|date=September 2007}}
== References ==
=== Inline ===
{{reflist|2}}


Preexisting hepatic (liver) and/or renal (kidney) damage or [[cancer]], [[hepatitis]], [[pancreatitis]], end-stage [[AIDS]] [[HIV]] infection, [[bone marrow]] depression, urea cycle disorders, and [[coagulation]] hematological disorders are absolute contraindications.
=== General ===
* [http://online.wsj.com/article/SB118798557326508182.html With 'LOLcats' Internet Fad, Anyone Can Get In on the Joke], [[Wall Street Journal]], 25<sup>th</sup> August 2007
* [http://www.nytimes.com/2007/07/21/business/21online.html?ex=1187668800&en=b63b5b4971bececb&ei=5070 Can Green Make Green?: New Media, New Methods], [[New York Times]], 21<sup>st</sup> July 2007
* [http://www.gazette.com/articles/cat_25284___article.html/sites_web.html If you give a cat a keyboard], [[Minneapolis Star Tribune]], 26<sup>th</sup> July 2007
* [http://www.businessweek.com/smallbiz/content/jul2007/sb20070713_202390.htm Bloggers Bring in the Big Bucks], [[BusinessWeek]], 13<sup>th</sup> July 2007
* [http://www.receiver.vodafone.com/19-oh-hai Oh Hai! Cats, the internet, and tactical communities.], Joshua Green in receiver magazine, Autumn 2007


==Adverse effects==
[[Category:Internet slang]]
Common [[adverse drug reaction|side effects]] are [[dyspepsia]] and/or weight gain. Less common are [[fatigue (medical)|fatigue]], [[peripheral edema]], [[dizziness]], drowsiness, [[hair loss]], headaches, [[nausea]], [[sedation]] and [[tremor]]s. Valproic acid also causes [[hyperammonemia]], which can lead to brain damage.<ref>[http://www.jabfm.org/cgi/content/abstract/20/5/499 Valproate-associated Hyperammonemic Encephalopathy - Wadzinski et al. 20 (5): 499 - The Journal of the American Board of Family Medicine<!-- Bot generated title -->]</ref> Valproate levels within the normal range are capable of causing hyperammonemia and ensuing [[encephalopathy]]. There have been reports of brain encephalopathy developing without hyperammonemia or elevated valproate levels.<ref>[http://www.thieme-connect.com/ejournals/abstract/neuropediatrics/doi/10.1055/s-2006-973995 Thieme-connect - Abstract<!-- Bot generated title -->]</ref>
[[Category:Internet memes]]
[[Category:Web humor]]
[[Category:Photography by genre]]
[[Category:Cats in popular culture]]


Rarely, valproic acid can cause [[dyscrasia|blood dyscrasia]], impaired [[liver]] function, [[jaundice]], [[thrombocytopenia]], and prolonged [[coagulation]] times. In about 5% of pregnant users, valproic acid will cross the [[placenta]] and cause [[congenital defect|congenital anomalies]]. Due to these side effects, most doctors will ask for blood tests, initially as often as once a week and then once every 2 months. Temporary liver enzyme increase has been reported in 20% of cases during the first few months of taking the drug. Inflammation of the liver ([[hepatitis]]), the first symptom of which is [[jaundice]], is found in rare cases.
[[da:Lolcat]]

[[es:Lolcat]]
Valproic acid may also cause acute hematological toxicities, especially in children, including rare reports of myelodysplasia and acute leukemia-like syndrome.<ref>{{cite journal | author = Williams DC Jr, Massey GV, Russell EC, Riley RS, Ben-Ezra J. | title = Translocation positive acute myeloid leukemia associated with valproic acid therapy | journal = [[Pediatric Blood and Cancer]] | volume = Mar 29 | issue = | pages = 641| year = 2007 | pmid = 17262798 | doi = 10.1002/pbc.21149}}</ref><ref>{{cite journal | author = Coyle TE, Bair AK, Stein C, Vajpayee N, Mehdi S, Wright J. | title = Acute leukemia associated with valproic acid treatment: a novel mechanism for leukemogenesis? | journal = [[Pediatric Blood and Cancer]] | volume = Apr | issue = 78 | pages = 256–60 | year = 2005 | pmid = 15795916 | doi = 10.1002/ajh.20273}}</ref>
[[fr:Lolcat]]

[[hu:Lolcat]]
There have also been reports of cognitive dysfunction, [[Parkinsonism]]<ref name="pmid15971646">{{cite journal |author=Ricard C, Martin K, Tournier M, Bégaud B, Verdoux H |title=[A case of Parkinsonian syndrome, cognitive impairment and hyperammonemia induced by divalproate sodium prescribed for bipolar disorder] |language=French |journal=L'Encéphale |volume=31 |issue=1 Pt 1 |pages=98–101 |year=2005 |pmid=15971646 |doi=}}</ref>, and even (reversible) pseudoatrophic brain changes<ref name="pmid3117347">{{cite journal |author=McLachlan RS |title=Pseudoatrophy of the brain with valproic acid monotherapy |journal=The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques |volume=14 |issue=3 |pages=294–6 |year=1987 |pmid=3117347 |doi=}}</ref> in long-term treatment with valproic acid.
[[nl:Lolcat]]

[[no:Lolcat]]
==Pharmacology==
[[pl:Lolcat]]
Valproate is believed to affect the function of the [[neurotransmitter]] [[GABA]] (as a [[transaminase|GABA transaminase]] inhibitor) in the human brain, making it an alternative to [[Lithium pharmacology|lithium salt]]s in treatment of bipolar disorder.In addition to blocking transamination of GABA, Valproate is believed to reverse the transamination process to form more GABA. However, several other mechanisms of action in neuropsychiatric disorders have been proposed for valproic acid in recent years.<ref>{{cite journal | author = Rosenberg G | title = The mechanisms of action of valproate in neuropsychiatric disorders: can we see the forest for the trees? | journal = [[Cellular and Molecular Life Sciences]] | year =2007 | pmid = 17514356 | volume = 64 | pages = 2090 | doi = 10.1007/s00018-007-7079-x}}</ref>.
[[ru:Lolcat]]

Valproic acid also blocks the [[voltage-gated sodium channel]]s and T-type Calcium channels.These mechanisms make Valproic Acid a Broad Spectrum Anticonvulsant drug.

Valproic acid is an [[Enzyme inhibitor|inhibitor]] of the [[enzyme]] [[histone deacetylase 1]] (HDAC1). It is a member of a larger class of [[histone deacetylase inhibitor]]s.

==Interactions==
Valproic acid may interact with [[carbamazepine]], as valproates inhibit [[epoxide hydrolase|microsomal epoxide hydrolase]] (mEH), the [[enzyme]] responsible for the breakdown of carbamazepine-10,11 epoxide (the main active metabolite of carbamazepine) into inactive metabolites.<ref>{{cite book |last=Gonzalez |first=Frank J. |coauthors=Robert H. Tukey |editor=Laurence Brunton, John Lazo, Keith Parker (eds.) |title=[[Goodman & Gilman's The Pharmacological Basis of Therapeutics]] |edition=11<sup>th</sup> ed. |year=2006 |publisher=[[McGraw-Hill]] |location=New York |isbn=978-0071422802|pages=p. 79 |chapter=Drug Metabolism }}</ref> By inhibiting mEH, valproic acid causes a buildup of the active metabolite, prolonging the effects of carbamazepine and delaying its excretion.

Valproic acid also decreases the [[clearance (medicine)|clearance]] of [[amitriptyline]] and [[nortriptyline]].<ref name="RxList">{{cite web | url = http://www.rxlist.com/cgi/generic/depakene_ad.htm | title = Depakene side effects (Valproic Acid) and drug interactions | year = 2007 | accessdate = 2007-06-07 | publisher = RxList.com}}</ref>

Also, Valproic acid should be used with caution with drugs like benzodiazopines and aspirin to avoid adverse effects.

==Formulations==
<!-- Please do not add sodium valproate-based products to this list. That drug has its own article -->
Branded products include:<br />
'''Depakene''' ([[Abbott Laboratories]] in U.S. & Canada)<br />
'''Convulex''' ([[Pfizer]] in the UK and Byk Madaus in South Africa)<br />
'''Stavzor''' ([[Noven Pharmaceuticals|Noven Pharmaceuticals Inc.]])<br />
'''Depakine''' ([[Sanofi Aventis|Sanofi Aventis.]]) <br />
'''Epival''' ([[Abbott Laboratories]] U.S. & Canada)

==References==
{{Reflist|2}}

==Further reading==
*T.R. Henry, "The History of Valproate in Clinical Neuroscience." [http://www.medworksmedia.com/psychopharmbulletin/pdf/19/1-PB_VOL%2037%20SUPPL%202.pdf ''Psychopharmacology bulletin'' (2003) 37 (Suppl 2):5-16] (More details on history)

==External links==
* [http://www.psychotropics.dk/usr_view_molecule.asp?ID=2372&backurl=Alphaindex%2Fview%5Falpha%2Easp%3FStartchar%3DD&backurlname=Alphabetical+index&historyline=&Catalogtype=A The Lundbeck Institute Guide to Psychotropics - Valproic acid]
* http://www.psycheducation.org/depression/meds/moodstabilizers.htm
* http://www.psycheducation.org/depression/meds/valproate.htm
* [http://ctd.mdibl.org/voc.go?voc=chem&termUI=Valproic+Acid The Comparative Toxicogenomics Database:Valproic Acid]
* [http://www.chemicalland21.com/lifescience/phar/VALPROIC%20ACID.htm Chemical Land21: Valproic Acid]
* [http://www.rxlist.com/cgi/generic2/depakene.htm RXList.com: Depakene (Valproic Acid)] (U.S.)
* [http://home.intekom.com/pharm/byk/convulex.html South African Electronic Package Inserts: Convulex]
* [http://www.medbroadcast.com/drug_info_list.asp?search_letter=VALPROIC%20ACID Med Broadcast.com: Valproic Acid] (Canadian)

{{Anticonvulsants}}

[[Category:Anticonvulsants]]
[[Category:Mood stabilizers]]
[[Category:Teratogens]]
[[Category:Carboxylic acids]]

[[de:Valproinsäure]]
[[es:Ácido valproico]]
[[fr:Acide valproïque]]
[[it:Acido valproico]]
[[no:Valproat]]
[[pl:Kwas walproinowy]]
[[pt:Valproato]]
[[ru:Вальпроевая кислота]]
[[sv:Valproinsyra]]

Revision as of 19:02, 12 October 2008

Valproate
Clinical data
License data
Pregnancy
category
Routes of
administration		Oral, intravenous
ATC code
Legal status
Legal status
Pharmacokinetic data
BioavailabilityRapid absorption
Protein bindingConcentration-dependent, from 90% at 40 µg/mL to 81.5% at 130 µg/mL
MetabolismHepatic—glucuronide conjugation 30–50%, mitochondrial β-oxidation over 40%
Elimination half-life9–16 hours
ExcretionLess than 3% excreted unchanged in urine.
Identifiers
  • 2-propylpentanoic acid
CAS Number
PubChem CID
DrugBank
CompTox Dashboard (EPA)
ECHA InfoCard100.002.525 Edit this at Wikidata
Chemical and physical data
FormulaC8H16O2
Molar mass144.211 g/mol g·mol−1
3D model (JSmol)
  • CCCC(CCC)C(=O)O

Valproic acid (VPA) is a chemical compound that has found clinical use as an anticonvulsant and mood-stabilizing drug, primarily in the treatment of epilepsy, bipolar disorder, and less commonly major depression. It is also used to treat migraine headaches and schizophrenia.

Related drugs include the sodium salts sodium valproate, used as an anticonvulsant, and a combined formulation, valproate semisodium, used as a mood stabilizer and additionally in the U.S. also as an anticonvulsant.

History

Valproic acid (by its official name 2-propylvaleric acid) was first synthesized in 1882 by Burton as an analogue of valeric acid, found naturally in valerian.[2] A clear liquid fatty acid at room temperature, for many decades its only use was in laboratories as a "metabolically inert" solvent for organic compounds. In 1962, the French researcher Pierre Eymard serendipitously discovered the anticonvulsant properties of valproic acid while using it as a vehicle for a number of other compounds that were being screened for anti-seizure activity. He found that it prevented pentylenetetrazol-induced convulsions in rodents.[3] Since then it has also been used for migraine and bipolar disorder.[4]

Indications

As an anticonvulsant, valproic acid is used to control absence seizures, tonic-clonic seizures (grand mal), complex partial seizures, juvenile myoclonic epilepsy and the seizures associated with Lennox-Gastaut syndrome. It is also used in treatment of myoclonus. In some countries, parenteral (administered intravenously) preparations of valproate are used also as second-line treatment of status epilepticus, as an alternative to phenytoin. Valproate is one of the most common drugs used to treat post-traumatic epilepsy.[5]

According to Medical News Today, valproic acid can be used for the treatment of manic episodes associated with bipolar disorder, adjunctive therapy in multiple seizure types (including epilepsy), and prophylaxis of migraine headaches[6]. It is more recently being used to treat neuropathic pain, as a second line agent, particularly lancinating pain from A* fibres.

Investigational

HDAC1 is needed for HIV to remain in infected cells. A study published in August 2005 found that three of four patients treated with valproic acid in addition to highly active antiretroviral therapy (HAART) showed a mean 75% reduction in latent HIV infection.[7] Subsequent trials, however, have found no long term benefits of valproic acid in HIV infection.[8]

According to the U.S. National Institutes of Health and others, valproic acid appears to have wide implications in the treatment of various cancers,[9] including multiple myeloma (bone marrow cancer),[10] glioma (an aggressive type of brain tumor),[11] and melanoma.[12] Valproic acid is cytotoxic to many different cancer types through its action as a histone-deacetylase inhibitor.

Another potential indication may be leukemia in juvenile patients. Studies conducted by several European centres are ongoing. Although it is too early to make a definitive statement, preliminary results are encouraging.[citation needed]

Contraindications

Valproate is relatively contraindicated in pregnancy due to its teratogenicity; women who become pregnant while taking valproate should be counselled as to its risks, take high dose folic acid and be offered antenatal screening (alpha-fetoprotein and second trimester ultrasound scans).[13] It is a known folate antagonist, which can cause neural tube defects. Thus, folic acid supplements may alleviate the teratogenic problems. A recent study showed that children of mothers taking valproate during pregnancy are at risk for significantly lower IQs.[14][15] Exposure of the human embryo to valproic acid is also associated with risk of autism, and it is possible to duplicate features characteristic of autism by exposing rat embryos to valproic acid at the time of neural tube closure.[16] One study found that valproate exposure on embryonic day 11.5 led to significant local recurrent connectivity in the juvenile rat neocortex, consistent with the underconnectivity theory of autism.[17]

Valproate is contraindicated in overweight patients because it might cause weight gain.[citation needed]

Preexisting hepatic (liver) and/or renal (kidney) damage or cancer, hepatitis, pancreatitis, end-stage AIDS HIV infection, bone marrow depression, urea cycle disorders, and coagulation hematological disorders are absolute contraindications.

Adverse effects

Common side effects are dyspepsia and/or weight gain. Less common are fatigue, peripheral edema, dizziness, drowsiness, hair loss, headaches, nausea, sedation and tremors. Valproic acid also causes hyperammonemia, which can lead to brain damage.[18] Valproate levels within the normal range are capable of causing hyperammonemia and ensuing encephalopathy. There have been reports of brain encephalopathy developing without hyperammonemia or elevated valproate levels.[19]

Rarely, valproic acid can cause blood dyscrasia, impaired liver function, jaundice, thrombocytopenia, and prolonged coagulation times. In about 5% of pregnant users, valproic acid will cross the placenta and cause congenital anomalies. Due to these side effects, most doctors will ask for blood tests, initially as often as once a week and then once every 2 months. Temporary liver enzyme increase has been reported in 20% of cases during the first few months of taking the drug. Inflammation of the liver (hepatitis), the first symptom of which is jaundice, is found in rare cases.

Valproic acid may also cause acute hematological toxicities, especially in children, including rare reports of myelodysplasia and acute leukemia-like syndrome.[20][21]

There have also been reports of cognitive dysfunction, Parkinsonism[22], and even (reversible) pseudoatrophic brain changes[23] in long-term treatment with valproic acid.

Pharmacology

Valproate is believed to affect the function of the neurotransmitter GABA (as a GABA transaminase inhibitor) in the human brain, making it an alternative to lithium salts in treatment of bipolar disorder.In addition to blocking transamination of GABA, Valproate is believed to reverse the transamination process to form more GABA. However, several other mechanisms of action in neuropsychiatric disorders have been proposed for valproic acid in recent years.[24].

Valproic acid also blocks the voltage-gated sodium channels and T-type Calcium channels.These mechanisms make Valproic Acid a Broad Spectrum Anticonvulsant drug.

Valproic acid is an inhibitor of the enzyme histone deacetylase 1 (HDAC1). It is a member of a larger class of histone deacetylase inhibitors.

Interactions

Valproic acid may interact with carbamazepine, as valproates inhibit microsomal epoxide hydrolase (mEH), the enzyme responsible for the breakdown of carbamazepine-10,11 epoxide (the main active metabolite of carbamazepine) into inactive metabolites.[25] By inhibiting mEH, valproic acid causes a buildup of the active metabolite, prolonging the effects of carbamazepine and delaying its excretion.

Valproic acid also decreases the clearance of amitriptyline and nortriptyline.[26]

Also, Valproic acid should be used with caution with drugs like benzodiazopines and aspirin to avoid adverse effects.

Formulations

Branded products include:
Depakene (Abbott Laboratories in U.S. & Canada)
Convulex (Pfizer in the UK and Byk Madaus in South Africa)
Stavzor (Noven Pharmaceuticals Inc.)
Depakine (Sanofi Aventis.)
Epival (Abbott Laboratories U.S. & Canada)

References

  1. ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 Oct 2023.
  2. ^ Burton BS (1882). On the propyl derivatives and decomposition products of ethylacetoacetate. Am Chem J. 3:385-395.
  3. ^ Meunier H, Carraz G, Meunier Y, Eymard P, Aimard M. (1963). Propriétés pharmacodynamiques de l’acide n-dipropylacetique. Therapie 18:435-438.
  4. ^ Henry T.R. (2003). The History of Valproate in Clinical Neuroscience. Psychopharmacology bulletin 37 (Suppl 2):5-16
  5. ^ Posner E, Lorenzo N (October 11, 2006). "Posttraumatic epilepsy". Emedicine.com. Retrieved on 2008-07-30.
  6. ^ "FDA Issues Approvable Letter For Stavzor Delayed Release Valproic Acid Capsules". 2007 MediLexicon International Ltd. 2007-10-25. Retrieved 2007-10-29. {{cite news}}: Cite has empty unknown parameter: |coauthors= (help)
  7. ^ Lehrman G, Hogue I, Palmer S, Jennings C, Spina C, Wiegand A, Landay A, Coombs R, Richman D, Mellors J, Coffin J, Bosch R, Margolis D (2005). "Depletion of latent HIV-1 infection in vivo: a proof-of-concept study". Lancet. 366 (9485): 549–55. doi:10.1016/S0140-6736(05)67098-5. PMID 16099290.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  8. ^ Sagot-Lerolle N, Lamine A, Chaix ML, Boufassa F, Aboulker JP, Costagliola D, Goujard C, Paller C, Delfraissy JF, Lambotte O; ANRS EP39 study (2008). "Prolonged valproic acid treatment does not reduce the size of latent HIV reservoir". AIDS. 22 (10): 1125–29. PMID 18525257.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: numeric names: authors list (link)
  9. ^ Isenberg JS, Jia Y, Field L, Ridnour LA, Sparatore A, Del Soldato P, Sowers AL, Yeh GC, Moody TW, Wink DA, Ramchandran R, Roberts DD (2007). "Modulation of angiogenesis by dithiolethione-modified NSAIDs and valproic acid". British Journal of Pharmacology. Mar 12. PMID 17273758.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  10. ^ Schwartz C, Palissot V, Aouali N, Wack S, Brons NH, Leners B, Bosseler M, Berchem G (2007). "Valproic acid induces non-apoptotic cell death mechanisms in multiple myeloma cell lines". International Journal of Oncology. Mar (30): 573–82. PMID 17273758.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  11. ^ A.M. Admirant, J. A. Hendricks, P.C. De Witt Hamer, S. Leenstra, W.P. Vandertop, C.J.F. van Noorden, and J.P. Medema (2006). "Valproic Acid is toxic to malignant glioma cells and increases sensitivity to irradiation and chemotherapy". Abstracts for the Seventh Congress of the European Association for Neuro-Oncology (EANO). Sept 14-17: 334. doi:10.1186/1476-4598-5-71,. {{cite journal}}: Check |doi= value (help); Unknown parameter |doi_brokendate= ignored (|doi-broken-date= suggested) (help)CS1 maint: extra punctuation (link) CS1 maint: multiple names: authors list (link)
  12. ^ Valentini A, Gravina P, Federici G, Bernardini S. (2007). "Valproic Acid Induces Apoptosis, p(16INK4A) Upregulation and Sensitization to Chemotherapy in Human Melanoma Cells". Cancer Biology & Therapy. Feb 5 (6). PMID 17218782.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  13. ^ British National Formulary (March 2003) 45
  14. ^ Cassels, Caroline (December 8 2006). "NEAD: In Utero Exposure To Valproate Linked to Poor Cognitive Outcomes in Kids". Medscape. Retrieved 2007-05-23. {{cite web}}: Check date values in: |date= (help)
  15. ^ Meador KJ, Baker GA, Finnell RH; et al. (2006). "In utero antiepileptic drug exposure: fetal death and malformations". Neurology. 67 (3): 407–12. doi:10.1212/01.wnl.0000227919.81208.b2. PMID 16894099. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  16. ^ Arndt TL, Stodgell CJ, Rodier PM (2005). "The teratology of autism". Int J Dev Neurosci. 23 (2–3): 189–99. doi:10.1016/j.ijdevneu.2004.11.001. PMID 15749245.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  17. ^ Rinaldi T, Silberberg G, Markram H (2007). "Hyperconnectivity of local neocortical microcircuitry induced by prenatal exposure to valproic acid". Cereb Cortex. 18: 763. doi:10.1093/cercor/bhm117. PMID 17638926.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  18. ^ Valproate-associated Hyperammonemic Encephalopathy - Wadzinski et al. 20 (5): 499 - The Journal of the American Board of Family Medicine
  19. ^ Thieme-connect - Abstract
  20. ^ Williams DC Jr, Massey GV, Russell EC, Riley RS, Ben-Ezra J. (2007). "Translocation positive acute myeloid leukemia associated with valproic acid therapy". Pediatric Blood and Cancer. Mar 29: 641. doi:10.1002/pbc.21149. PMID 17262798.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  21. ^ Coyle TE, Bair AK, Stein C, Vajpayee N, Mehdi S, Wright J. (2005). "Acute leukemia associated with valproic acid treatment: a novel mechanism for leukemogenesis?". Pediatric Blood and Cancer. Apr (78): 256–60. doi:10.1002/ajh.20273. PMID 15795916.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  22. ^ Ricard C, Martin K, Tournier M, Bégaud B, Verdoux H (2005). "[A case of Parkinsonian syndrome, cognitive impairment and hyperammonemia induced by divalproate sodium prescribed for bipolar disorder]". L'Encéphale (in French). 31 (1 Pt 1): 98–101. PMID 15971646.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  23. ^ McLachlan RS (1987). "Pseudoatrophy of the brain with valproic acid monotherapy". The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques. 14 (3): 294–6. PMID 3117347.
  24. ^ Rosenberg G (2007). "The mechanisms of action of valproate in neuropsychiatric disorders: can we see the forest for the trees?". Cellular and Molecular Life Sciences. 64: 2090. doi:10.1007/s00018-007-7079-x. PMID 17514356.
  25. ^ Gonzalez, Frank J. (2006). "Drug Metabolism". In Laurence Brunton, John Lazo, Keith Parker (eds.) (ed.). Goodman & Gilman's The Pharmacological Basis of Therapeutics (11th ed. ed.). New York: McGraw-Hill. pp. p. 79. ISBN 978-0071422802. {{cite book}}: |edition= has extra text (help); |editor= has generic name (help); |pages= has extra text (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)CS1 maint: multiple names: editors list (link)
  26. ^ "Depakene side effects (Valproic Acid) and drug interactions". RxList.com. 2007. Retrieved 2007-06-07.

Further reading

External links

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