Valnoctamide

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Valnoctamide
Skeletal formula of valnoctamide
Identifiers
CAS number 4171-13-5 N
PubChem 20140, 36689722 2R,3R, 10313196 2R,3S, 25271745 2S,3R, 12015994 2S,3S
ChemSpider 18974 YesY, 8488661 2R,3S YesY
UNII 3O25NRX9YG YesY
EC number 224-033-7
KEGG D02717 N
MeSH valnoctamide
ChEMBL CHEMBL1075733 YesY
RTECS number YV5950000
ATC code N05CM13
Jmol-3D images Image 1
Image 2
Properties
Molecular formula C8H17NO
Molar mass 143.23 g mol−1
Appearance White crystals
log P 1.885
Pharmacology
Bioavailability 94%
Routes of
administration
  • Intravenous
  • Oral
Metabolism Hepatic
Elimination
half-life
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
GHS hazard statements H302
EU classification Harmful Xn
R-phrases R22
LD50 760 mg kg−1 (oral, rat)
Related compounds
Related alkanamides Valpromide
Related compounds
Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
 N (verify) (what is: YesY/N?)
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 since 1969[4] and was still being investigated in 2000[5] and 2003.

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.[6]

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.[7]

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.[8]

Chemistry[edit]

Valnoctamide is a racemic compound with four stereoisomers,[9] 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.[10]

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, and 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. ^ Winkler, Ilan; Simcha Blotnik, Jakob Shimshoni, Boris Yagen, Marshall Devor, and 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 1576263. PMID 15997234. 
  7. ^ RH Belmaker, Yuly Bersudsky, Alex Mishory and Beersheva Mental Health Center (2005). "Valnoctamide in Mania". ClinicalTrials.gov. United States National Institutes of Health. Retrieved 25 February 2006. 
  8. ^ 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. PMC 1381382. PMID 1352988. 
  9. ^ 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
  10. ^ 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 8 (8): 1293–1301. doi:10.1023/A:1025069519218. PMID 12948028.