Valnoctamide

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Valnoctamide
Skeletal formula of valnoctamide
Valnoctamide3D.gif
Names
IUPAC name
2-Ethyl-3-methylpentanamide[1]
Identifiers
3D model (JSmol)
ChEMBL
ChemSpider
ECHA InfoCard 100.021.849
EC Number 224-033-7
KEGG
MeSH valnoctamide
RTECS number YV5950000
UNII
Properties
C8H17NO
Molar mass 143.23 g·mol−1
Appearance White crystals
log P 1.885
Pharmacology
N05CM13 (WHO)
  • Intravenous
  • Oral
Pharmacokinetics:
94%
Hepatic
10 hours
Hazards
GHS pictograms The exclamation-mark pictogram in the Globally Harmonized System of Classification and Labelling of Chemicals (GHS)
GHS signal word WARNING
H302
Lethal dose or concentration (LD, LC):
760 mg kg−1 (oral, rat)
Related compounds
Related alkanamides
Valpromide
Related compounds
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references

Valnoctamide (INN, USAN) has been used in France as a sedative-hypnotic since 1964.[2] It is a structural isomer of valpromide, a valproic acid prodrug; unlike valpromide, however, valnoctamide is not transformed into its homologous acid, valnoctic acid, in vivo.[3]

Indications[edit]

In addition to being a sedative, valnoctamide has been investigated for use in epilepsy.[4][5][6]

It was studied for neuropathic pain in 2005 by Winkler et al., with good results: it had minimal effects on motor coordination and alertness at effective doses, and appeared to be equally effective as gabapentin.[7]

RH Belmaker, Yuly Bersudsky and Alex Mishory started a clinical trial of valnoctamide for prophylaxis of mania in lieu of the much more teratogenic valproic acid or its salts.[8]

Side effects[edit]

The side effects of valnoctamide are mostly minor and include somnolence and the slight motor impairments mentioned above.

Interactions[edit]

Valnoctamide is known to increase through inhibition of epoxide hydrolase the serum levels of carbamazepine-10,11-epoxide, the active metabolite of carbamazepine, sometimes to toxic levels.[9]

Chemistry[edit]

Valnoctamide is a racemic compound with four stereoisomers,[10] all of which were shown to be more effective than valproic acid in animal models of epilepsy and one of which [(2S,3S]-valnoctamide) was considered to be a good candidate by Isoherranen, et al. for an anticonvulsant in August 2003.[11]

Butabarbital can be hydrolyzed to Valnoctamide.[12]

References[edit]

  1. ^ "valnoctamide - Compound Summary". PubChem Compound. USA: National Center for Biotechnology Information. 26 March 2005. Identification and Related Records. Retrieved 20 February 2012. 
  2. ^ Harl, F. M. (March 1964). "[Clinical Study Of Valnoctamide On 70 Neuropsychiatric Clinic Patients Undergoing Ambulatory Treatment]". La Presse Médicale (in French). 72: 753–754. PMID 14119722. 
  3. ^ Haj-Yehia, Abdullah; Meir Bialer (August 1989). "Structure-pharmacokinetic relationships in a series of valpromide derivatives with antiepileptic activity". Pharmaceutical Research. 6 (8): 683–689. doi:10.1023/A:1015934321764. PMID 2510141. 
  4. ^ Mattos Nda, S. (May 1969). "[Use of Valnoctamide (nirvanil) in oligophrenic erethics and epileptics]". Hospital (Rio J) (in Portuguese). 75 (5): 1701–1704. PMID 5306499. 
  5. ^ Lindekens, H.; Ilse Smolders; Ghous M. Khan; Meir Bialer; Guy Ebinger; Yvette Michotte (November 2000). "In vivo study of the effect of valpromide and valnoctamide in the pilocarpine rat model of focal epilepsy". Pharmaceutical Research. 17 (11): 1408–1413. doi:10.1023/A:1007559208599. PMID 11205735. 
  6. ^ Rogawski, MA (2006). "Diverse mechanisms of antiepileptic drugs in the development pipeline". Epilepsy Res. 69 (3): 273–294. doi:10.1016/j.eplepsyres.2006.02.004. PMC 1562526Freely accessible. PMID 16621450. 
  7. ^ Winkler, Ilan; Simcha Blotnik; Jakob Shimshoni; Boris Yagen; Marshall Devor; Meir Bialer (September 2005). "Efficacy of antiepileptic isomers of valproic acid and valpromide in a rat model of neuropathic pain". British Journal of Pharmacology. 146 (2): 198–208. doi:10.1038/sj.bjp.0706310. PMC 1576263Freely accessible. PMID 15997234. 
  8. ^ RH Belmaker; Yuly Bersudsky; Alex Mishory; Beersheva Mental Health Center (2005). "Valnoctamide in Mania". ClinicalTrials.gov. United States National Institutes of Health. Retrieved 25 February 2006. 
  9. ^ Pisani, F; Fazio, A; Artesi, C; Oteri, G; Spina, E; Tomson, T; Perucca, E (1992). "Impairment of carbamazepine-10, 11-epoxide elimination by valnoctamide, a valpromide isomer, in healthy subjects". British Journal of Clinical Pharmacology. 34 (1): 85–87. doi:10.1111/j.1365-2125.1992.tb04114.x. PMC 1381382Freely accessible. PMID 1352988. 
  10. ^ Shimon Barel, Boris Yagen, Volker Schurig, Stephan Sobak, Francesco Pisani, Emilio Perucca and Meir Bialer. Stereoselective pharmacokinetic analysis of valnoctamide in healthy subjects and in patients with epilepsy. Clinical Pharmacology & Therapeutics 61, 442–449 (April 1997) doi:10.1016/S0009-9236(97)90194-6
  11. ^ Isoherranen, Nina; H. Steve White; Brian D. Klein; Michael Roeder; José H. Woodhead; Volker Schurig; Boris Yagen; Meir Bialer (August 2003). "Pharmacokinetic-pharmacodynamic relationships of (2S,3S)-valnoctamide and its stereoisomer (2R,3S)-valnoctamide in rodent models of epilepsy". Pharmaceutical Research. 20 (8): 1293–1301. doi:10.1023/A:1025069519218. PMID 12948028. 
  12. ^ Freifelder, Morris; Geiszler, Adolph O.; Stone, George R. (1961). "Hydrolysis of 5,5-Disubstituted Barbituric Acids". The Journal of Organic Chemistry. 26 (1): 203–206. doi:10.1021/jo01060a048. ISSN 0022-3263.