Valnoctamide

Structural formula
(2 R , 3 R ) -isomer (top, left), (2 S , 3 S ) -isomer (top, right), (2 S , 3 R ) -isomer (bottom, left) and (2 R , 3 S ) isomer (bottom, right)
General
Non-proprietary name	Valnoctamide
other names	2-ethyl-3-methylpentanamide 2-ethyl-3-methylvaleramide
Molecular formula	C 8 H 17 NO
External identifiers / databases
CAS number 4171-13-5 (mixture of stereoisomers) 189189-74-0 [(2 R , 3 R ) -isomer] 189189-75-1 [(2 S , 3 S ) -isomer] 189189-73-9 [(2 S , 3 R ) -isomer] 189189-76-2 [(2 R , 3 S ) -isomer] EC number 224-033-7 ECHA InfoCard 100,021,849 PubChem 20140 ChemSpider 18974 DrugBank DB13099 Wikidata Q410468
Drug information
ATC code	N05 CM13
Drug class	Hypnotic , sedative
properties
Molar mass	143.23 g · mol -1
Physical state	firmly
Melting point	113.5–114 ° C ( mixture of stereoisomers)
safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed GHS labeling of hazardous substances Caution H and P phrases H: 302 P: no P-phrases
Toxicological data	760 mg kg −1 ( LD 50 ,  rat ,  oral ) 540 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 .

Valnoctamide is a mixture of several chemical compounds from the group of carboxamides , which has been in use in France as a sleep aid and sedative since 1964 . The drug valnoctamide is a structural isomer of valpromide , a prodrug precursor of valproic acid . In contrast to valpromide, however, valnoctamide is not converted into the corresponding carboxylic acid in the body .

Areas of application

In addition to its effects as a sedative, valnoctamide has been studied as an anti- epilepsy agent since 1969 . Investigations in this direction continued in 2000 and 2003.

As a remedy for neuropathic pain , it was published in 2005 by Winkler et al. studied with encouraging results: it showed minimal effects on coordination and attention at effective doses and appeared to be as effective as gabapentin .

RH Belmaker, Yuly Bersudsky and Alex Mishory started a clinical study of valnoctamide as a replacement medication for the much more teratogenic valproic acid and its salts for the prophylaxis of mania .

Side effects

The known side effects of valnoctamide are mostly negligible and consist of somnolence and slight coordination disorders .

Contraindications

Valnoctamide increases the serum concentration of carbamazepine-10,11-epoxide, the active metabolite of carbamazepine , sometimes to toxic levels because it inhibits epoxide hydrolase .

chemistry

Valnoctamide is a chiral drug which , because of its two stereogenic centers (in the 2- and 3-position), has four stereoisomers : the (2 R , 3 R ) form and the corresponding enantiomeric (2 S , 3 S ) form as well as the (2 S , 3 R ) -isomer and the (2 R , 3 S ) -isomer. The mixture of the four stereoisomers is used as the medicinal substance . Each of the stereoisomers is more effective against epilepsy than valproic acid in the animal model, and one of them - (2 S , 3 S ) valnoctamide - was discovered by Isoherranen et al. In August 2003. described as a good candidate for an anticonvulsant .

Individual evidence

1. ^ The Merck Index . An Encyclopaedia of Chemicals, Drugs and Biologicals . 14th edition, 2006, p. 1704, ISBN 978-0-911910-00-1 .
2. ↑ ^{a b} Valnoctamide data sheet from Sigma-Aldrich , accessed on April 25, 2011 ( PDF ).
3. ↑ ^{a b} Entry on valnoctamide in the ChemIDplus database of the United States National Library of Medicine (NLM) .
4. ↑ FM Harl: Clinical Study Of Valnoctamide On 70 Neuropsychiatric Clinic Patients Undergoing Ambulatory Treatment , La Presse Médicale 72, 753-4, 1964, PMID 14119722 .
5. ^ Abdullah Haj-Yehia, Meir Bialer: Structure-pharmacokinetic relationships in a series of valpromide derivatives with antiepileptic activity , Pharmaceutical Research 6, 683-9, 1989, PMID 2510141 , doi : 10.1023 / A: 1015934321764 .
6. ^ S. Mattos Nda: Use of Valnoctamide (nirvanil) in oligophrenic erethics and epileptics. , Hospital (Rio J) 75, 1701-4, 1969, PMID 5306499 .
7. ↑ Hilde Lindekens, Ilse Smolders, Ghous M. Khan, Meir Bialer, Guy Ebinger, Yvette Michotte: In vivo study of the effect of valpromide and valnoctamide in the pilocarpine rat model of focal epilepsy , Pharmaceutical Research 17, 1408-13, 2000, PMID 11205735 , doi : 10.1023 / A: 1007559208599 .
8. ↑ Ilan Winkler, Simcha Blotnik, Jakob Shimshoni, Boris Yagen, Marshall Devor, Meir Bialer: Efficacy of antiepileptic isomers of valproic acid and valpromide in a rat model of neuropathic pain , British Journal of Pharmacology 146, 198, 2005, PMID 15997234 , doi : 10.1038 / sj.bjp.0706310 .
9. ^ R. H Belmaker, Yuly Bersudsky, Alex Mishory: Valnoctamide in Mania , Beersheva Mental Health Center, 2005.
10. ↑ VALNOCTAMIDE Biam .
11. ↑ F. Pisani, A. Fazio, C. Artesi, G. Oteri, E. Spina, T. Tomson, E. Perucca: Impairment of carbamazepine-10,11-epoxide elimination by valnoctamide, a valpromide isomer, in healthy subjects. , British Journal of Clinical Pharmacology 34, 85-7, 1992, PMID 1352988 .
12. ↑ Nina Isoherranen, H. Steve White, Brian D. Klein, Michael Roeder, José H. Woodhead, Volker Schurig , Boris Yagen, Meir Bialer: Pharmacokinetic-pharmacodynamic relationships of (2S, 3S) -valnoctamide and its stereoisomer (2R, 3S ) -valnoctamide in rodent models of epilepsy , Pharmaceutical Research 8, 1293-1301, 2003, PMID 12948028 , doi : 10.1023 / A: 1025069519218 .

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