Phenelzine

Structural formula
General
Non-proprietary name	Phenelzine
other names	2-phenylethylhydrazine ( IUPAC ); Phenelzinum ( Latin );
Molecular formula	C 8 H 12 N 2
Brief description	white solid (sulfate)
External identifiers / databases
ECHA InfoCard	100,000,108
PubChem	3675
DrugBank	DB00780
Wikidata	Q1747559
Drug information
ATC code	N06 AF03
Drug class	antidepressant
Mechanism of action	irreversible monoamine oxidase inhibitor
properties
Molar mass	136.19 g · mol -1
Physical state	liquid
Melting point	174 ° C (hydrochloride)
boiling point	74 ° C (in vacuum)
solubility	soluble in water (sulfate); practically insoluble in ethanol , chloroform , diethyl ether (sulfate);
Refractive index	1.5494 (20 ° C)
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances sulfate danger
H and P phrases	H: 301
	P: 301 + 310
Toxicological data	210 mg kg −1 ( LD 50 , rat , oral ) ; 160 mg kg −1 ( LD 50 , mouse , oral ) ; 135 mg kg −1 ( LD 50 , mouse , ip ) ;
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions . Refractive index: Na-D line , 20 ° C

Phenelzine is a non-selective, irreversible monoamine oxidase inhibitor (MAOI) of the hydrazine class. It is used as an antidepressant and anxiolytic . Together with tranylcypromine and isocarboxazid , phenelzine is one of the few non-selective MAOIs.

Phenelzine is currently not available in Germany.

application areas

Phenelzine is mainly used for depressive disorders. Patients with “atypical”, “non-endogenous” and / or “neurotic” depressive symptoms react particularly well to phenelzine. The drug is also used successfully in patients who are unresponsive to conventional antidepressants or who have shown themselves to be "resistant to treatment".

In addition to treating major depressive disorder, it is also successfully used in the treatment of dysthymia , bipolar depression, panic disorder , social phobia , bulimia, and post-traumatic stress disorder (PTSD).

Mode of action

Phenelzine is a non-selective and irreversible inhibitor of the enzyme monoamine oxidase (MAO). It inhibits both the respective isoforms of MAO, MAO-A and MAO-B, almost equally, with a slight preference for the former. By inhibiting phenelzine, it prevents the breakdown of the monoamine neurotransmitters serotonin , melatonin , noradrenaline , adrenaline and dopamine , as well as the neuromodulators phenylethylamine , tyramine , octopamine and tryptamine . This leads to an increase in the extracellular concentrations of the respective messenger substances.

Interactions

The combination with sympathomimetics ( ephedrine , amphetamine ), reserpine leads to an uncontrolled increase in effectiveness with the risk of a high blood pressure crisis. Foods containing tyramine (aged cheese, red wine, etc.) can trigger hypertensive crises (low-tyramine diet necessary). A serotonin syndrome can develop in combination therapy with certain drugs that increase serotonin activity (selective serotonin reuptake inhibitors , venlafaxine , tricyclic antidepressants , 5-HT ₁ agonists).

The interactions of irreversible MAO inhibitors with anesthetics have been reported in individual cases (unstable circulation, comatose states). Simultaneous use with MAO inhibitors is generally described as a contraindication for almost all opioid preparations. There should be at least 14 days between the use of MAOIs and opioids. Particular care should be taken with tramadol , pethidine , fentanyl and also dextromethorphan .

A vitamin B6 deficiency can occur when taking phenelzine . Phenelzine and its metabolites (phenylethylidene hydrazine) react with vitamin B6 to form a biologically inert metabolite. For this reason, supplementation with vitamin B6 in the form of pyridoxine while taking phenelzine is recommended.

Unwanted side effects

Common side effects may include dizziness , blurred vision, dry mouth , headache, lethargy, sedation, somnolence , insomnia, loss of appetite, weight gain or loss, nausea and vomiting, diarrhea, constipation, urinary retention, mydriasis , muscle tremors, hyperthermia and sweating, high blood pressure or hypotension , orthostatic pressure Hypotension, paresthesia, hepatitis, and sexual dysfunction may occur. Hypomania or mania , psychosis and acute liver failure have been described as rare side effects .

Trade names

Monopreparations

Nardil (USA), Nardelzine (GB, ES, BE)

credentials

↑ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ Entry on phenelzine in the Hazardous Substances Data Bank , accessed on May 17, 2014.
^ S. Gangolli, Royal Society of Chemistry (Great Britain): The Dictionary of Substances and Their Effects: OS . Royal Society of Chemistry, 1999, ISBN 0-85404-833-2 , pp. 194 ( limited preview in Google Book search).
↑ ^a ^b Datasheet Phenelzine sulfate salt from Sigma-Aldrich , accessed on May 25, 2017 ( PDF ).
^ Parke-Davis Division of Pfizer Inc. (2007). Nardil (R) (Phenelzine sulfate tablets, USP) , labeling information. Retrieved December 14, 2009 from the US Food and Drug Administration's Web site.
↑ Fiedorowicz, JG; Swartz, KL (2004). The Role of Monoamine Oxidase Inhibitors in Current Psychiatric Practice . In: Journal of Psychiatric Practice ; 10: 239-248. doi : 10.1097 / 00131746-200407000-00005 . PMC 2075358 (free full text). PMID 15552546
^ Vallejo, J .; Gasto, C .; Catalan, R .; Salamero, M. (1987). Double-blind study of imipramine versus phenelzine in Melancholias and Dysthymic Disorders . In: The British Journal of Psychiatry ; 151: 639-642. doi : 10.1192 / bjp.151.5.639 . PMID 3446308
↑ Quitkin, FM; Mcgrath, P .; Liebowitz, MR; Stewart, J .; Howard, A. (1981). Monoamine oxidase inhibitors in bipolar endogenous depressives . In: Journal of Clinical Psychopharmacology ; 1: 70-74. doi : 10.1097 / 00004714-198103000-00005 . PMID 7028797
↑ Buigues, J .; Vallejo, J. (1987). Therapeutic response to phenelzine in patients with panic disorder and agoraphobia with panic attacks . In: Journal of Clinical Psychiatry ; 48: 55-59. PMID 3542985
↑ Blanco, C .; Schneier, F .; Schmidt, A .; Blanco-Jerez, C .; Marshall, R .; Sánchez-Lacay, A .; Liebowitz, M. (2003). Pharmacological treatment of social anxiety disorder: a meta-analysis . In: Depression and Anxiety ; 18: 29-40. doi : 10.1002 / da.10096 . PMID 12900950
↑ Walsh, BT; Gladis, M .; Roose, SP; Stewart, JW; Stetner, F .; Glassman, AH (1988). Phenelzine vs placebo in 50 patients with bulimia . In: Archives of General Psychiatry ; 45: 471-475. doi : 10.1001 / archpsyc.1988.01800290091011 . PMID 3282482
↑ Frank, JB; Cost, TR; Giller El, EL; Dan, E. (1988). A randomized clinical trial of phenelzine and imipramine for posttraumatic stress disorder . In: The American Journal of Psychiatry ; 145: 1289-1291. PMID 3048121
↑ RED HAND LETTER Serotonin Syndrome with Fentanyl
↑ Walter E. Haefeli: Interactions in pain therapy with opioids. ( Memento of the original from November 29, 2014 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. Forum Pain Bulletin 2011. @1@ 2

[HSDB-1] ↑ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ Entry on phenelzine in the Hazardous Substances Data Bank , accessed on May 17, 2014.

[S._Gangolli,_Royal_Society_of_Chemistry_(Great_Britain)-2] S. Gangolli, Royal Society of Chemistry (Great Britain): The Dictionary of Substances and Their Effects: OS . Royal Society of Chemistry, 1999, ISBN 0-85404-833-2 , pp. 194 ( limited preview in Google Book search).

[Sigma-3] Datasheet Phenelzine sulfate salt from Sigma-Aldrich , accessed on May 25, 2017 ( PDF ).

[4] Parke-Davis Division of Pfizer Inc. (2007). Nardil (R) (Phenelzine sulfate tablets, USP) , labeling information. Retrieved December 14, 2009 from the US Food and Drug Administration's Web site.

[5] Fiedorowicz, JG; Swartz, KL (2004). The Role of Monoamine Oxidase Inhibitors in Current Psychiatric Practice . In: Journal of Psychiatric Practice ; 10: 239-248. doi : 10.1097 / 00131746-200407000-00005 . PMC 2075358 (free full text). PMID 15552546

[6] Vallejo, J .; Gasto, C .; Catalan, R .; Salamero, M. (1987). Double-blind study of imipramine versus phenelzine in Melancholias and Dysthymic Disorders . In: The British Journal of Psychiatry ; 151: 639-642. doi : 10.1192 / bjp.151.5.639 . PMID 3446308

[7] Quitkin, FM; Mcgrath, P .; Liebowitz, MR; Stewart, J .; Howard, A. (1981). Monoamine oxidase inhibitors in bipolar endogenous depressives . In: Journal of Clinical Psychopharmacology ; 1: 70-74. doi : 10.1097 / 00004714-198103000-00005 . PMID 7028797

[8] Buigues, J .; Vallejo, J. (1987). Therapeutic response to phenelzine in patients with panic disorder and agoraphobia with panic attacks . In: Journal of Clinical Psychiatry ; 48: 55-59. PMID 3542985

[9] Blanco, C .; Schneier, F .; Schmidt, A .; Blanco-Jerez, C .; Marshall, R .; Sánchez-Lacay, A .; Liebowitz, M. (2003). Pharmacological treatment of social anxiety disorder: a meta-analysis . In: Depression and Anxiety ; 18: 29-40. doi : 10.1002 / da.10096 . PMID 12900950

[10] Walsh, BT; Gladis, M .; Roose, SP; Stewart, JW; Stetner, F .; Glassman, AH (1988). Phenelzine vs placebo in 50 patients with bulimia . In: Archives of General Psychiatry ; 45: 471-475. doi : 10.1001 / archpsyc.1988.01800290091011 . PMID 3282482

[11] Frank, JB; Cost, TR; Giller El, EL; Dan, E. (1988). A randomized clinical trial of phenelzine and imipramine for posttraumatic stress disorder . In: The American Journal of Psychiatry ; 145: 1289-1291. PMID 3048121

[12] RED HAND LETTER Serotonin Syndrome with Fentanyl

[13] Walter E. Haefeli: Interactions in pain therapy with opioids. ( Memento of the original from November 29, 2014 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. Forum Pain Bulletin 2011. @1@ 2