Valnoctamide

Last updated
Valnoctamide
Valnoctamide.svg
Valnoctamide3D.gif
Names
Preferred IUPAC name
2-Ethyl-3-methylpentanamide [1]
Identifiers
3D model (JSmol)
ChEMBL
ChemSpider
ECHA InfoCard 100.021.849 OOjs UI icon edit-ltr-progressive.svg
EC Number
  • 224-033-7
KEGG
MeSH valnoctamide
PubChem CID
RTECS number
  • YV5950000
UNII
  • InChI=1S/C8H17NO/c1-4-6(3)7(5-2)8(9)10/h6-7H,4-5H2,1-3H3,(H2,9,10) Yes check.svgY
    Key: QRCJOCOSPZMDJY-UHFFFAOYSA-N Yes check.svgY
  • CCC(C)C(CC)C(N)=O
Properties
C8H17NO
Molar mass 143.230 g·mol−1
AppearanceWhite crystals
log P 1.885
Pharmacology
N05CM13 ( WHO )
  • Intravenous
  • Oral
Pharmacokinetics:
94%
Hepatic
10 hours
Hazards
GHS labelling:
GHS-pictogram-exclam.svg
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).
X mark.svgN  verify  (what is  Yes check.svgYX mark.svgN ?)

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]

Contents

Indications

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

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

Interactions

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

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]

Related Research Articles

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Carbamazepine, sold under the brand name Tegretol among others, is an anticonvulsant medication used in the treatment of epilepsy and neuropathic pain. It is used as an adjunctive treatment in schizophrenia along with other medications and as a second-line agent in bipolar disorder. Carbamazepine appears to work as well as phenytoin and valproate for focal and generalized seizures. It is not effective for absence or myoclonic seizures.

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Anticonvulsants are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of bipolar disorder and borderline personality disorder, since many seem to act as mood stabilizers, and for the treatment of neuropathic pain. Anticonvulsants suppress the excessive rapid firing of neurons during seizures. Anticonvulsants also prevent the spread of the seizure within the brain.

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References

  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. S2CID   21531402.
  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. S2CID   24229165.
  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   1562526 . 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   1576263 . 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   1381382 . PMID   1352988.
  10. Shimon Barel, Boris Yagen, Volker Schurig, Stephan Sobak, Francesco Pisani, Emilio Perucca and Meir Bialer (1997). "Stereoselective pharmacokinetic analysis of valnoctamide in healthy subjects and in patients with epilepsy". Clinical Pharmacology & Therapeutics. 61 (4): 442–449. doi:10.1016/S0009-9236(97)90194-6. PMID   9129561.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  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. S2CID   20755032.
  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.