Valnoctamide

Valnoctamide
	File:Valnoctamide.svg
Clinical data
Routes of; administration	Oral, intravenous
ATC code	N05CM13 (WHO) ;
Legal status
Legal status	Not a controlled substance;
Pharmacokinetic data
Bioavailability	94%
Metabolism	Hepatic
Elimination half-life	10 hours
Identifiers
	IUPAC name 2-ethyl-3-methyl-pentanamide;
CAS Number	4171-13-5;
PubChem CID	20140;
E number	{{#property:P628}}
ECHA InfoCard	{{#property:P2566}}Lua error in Module:EditAtWikidata at line 36: attempt to index field 'wikibase' (a nil value).
Chemical and physical data
Formula	C8H17NO
Molar mass	143.227 g/mol

Valnoctamide (INN, USAN) has been used in France as an 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

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

The side effects of valnoctamide are mostly minor and include somnolence^[8] 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, 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 of 2003.^[10]

Notes and references

↑ Haj-Yehia, Abdullah (1988). "Pharmacokinetics of a valpromide isomer, valnoctamide, in dogs". Journal of Pharmaceutical Science. 77 (10): 831–4. PMID 3148708. Unknown parameter |coauthors= ignored (help); Unknown parameter |month= ignored (help)
↑ Template:Fr icon HARL, F. M. (1964). "[CLINICAL STUDY OF VALNOCTAMIDE ON 70 NEUROPSYCHIATRIC CLINIC PATIENTS UNDERGOING AMBULATORY TREATMENT.]". La Presse Médicale. 72: 753-4. PMID 14119722. Unknown parameter |month= ignored (help)
↑ Haj-Yehia, Abdullah (1989). "Structure-pharmacokinetic relationships in a series of valpromide derivatives with antiepileptic activity". Pharmaceutical Research. 6 (8): 683–9. PMID 2510141. Unknown parameter |coauthors= ignored (help); Unknown parameter |month= ignored (help)
↑ Template:Pt icon Mattos Nda, S. (1969). "[Use of Valnoctamide (nirvanil) in oligophrenic erethics and epileptics.]". Hospital (Rio J). 75 (5): 1701–4. PMID 5306499. Unknown parameter |month= ignored (help)
↑ Lindekens (2000). "In vivo study of the effect of valpromide and valnoctamide in the pilocarpine rat model of focal epilepsy". Pharmaceutical Research. 17 (11): 1408–13. PMID 11205735. Text " Hilde " ignored (help); Unknown parameter |coauthors= ignored (help); Unknown parameter |month= ignored (help)
↑ Winkler, Ilan (2005). "Efficacy of antiepileptic isomers of valproic acid and valpromide in a rat model of neuropathic pain". British Journal of Pharmacology. PMID 15997234. Unknown parameter |coauthors= ignored (help); Unknown parameter |month= ignored (help)
↑ RH Belmaker, Yuly Bersudsky, Alex Mishory and Beersheva Mental Health Center (2005). "Valnoctamide in Mania". ClinicalTrials.gov. United States National Institutes of Health. Unknown parameter |accessyear= ignored (|access-date= suggested) (help); Unknown parameter |accessdaymonth= ignored (help)
↑ VALNOCTAMIDE Biam French.
↑ Pisani F, Fazio A, Artesi C, Oteri G, Spina E, Tomson T, Perucca E. "Impairment of carbamazepine-10, 11-epoxide elimination by valnoctamide, a valpromide isomer, in healthy subjects." British Journal of Clinical Pharmacology. 1992 Jul;34(1):85-7. PMID 1352988
↑ Isoherranen, Nina (2003). "Pharmacokinetic-pharmacodynamic relationships of (2S,3S)-valnoctamide and its stereoisomer (2R,3S)-valnoctamide in rodent models of epilepsy". Pharmaceutical Research. 8 (8): 1293–301. PMID 12948028. Unknown parameter |coauthors= ignored (help); Unknown parameter |month= ignored (help)

External links

Template:Anticonvulsants

de:valnoctamide no:valnoktamid

Template:WikiDoc Sources

[bioavailability-1] Haj-Yehia, Abdullah (1988). "Pharmacokinetics of a valpromide isomer, valnoctamide, in dogs". Journal of Pharmaceutical Science. 77 (10): 831–4. PMID 3148708. Unknown parameter |coauthors= ignored (help); Unknown parameter |month= ignored (help)

[Harl_1964-2] Template:Fr icon HARL, F. M. (1964). "[CLINICAL STUDY OF VALNOCTAMIDE ON 70 NEUROPSYCHIATRIC CLINIC PATIENTS UNDERGOING AMBULATORY TREATMENT.]". La Presse Médicale. 72: 753-4. PMID 14119722. Unknown parameter |month= ignored (help)

[not-into-vpa-3] Haj-Yehia, Abdullah (1989). "Structure-pharmacokinetic relationships in a series of valpromide derivatives with antiepileptic activity". Pharmaceutical Research. 6 (8): 683–9. PMID 2510141. Unknown parameter |coauthors= ignored (help); Unknown parameter |month= ignored (help)

[Mattos_Nda_1969-4] Template:Pt icon Mattos Nda, S. (1969). "[Use of Valnoctamide (nirvanil) in oligophrenic erethics and epileptics.]". Hospital (Rio J). 75 (5): 1701–4. PMID 5306499. Unknown parameter |month= ignored (help)

[Lindekens_et_al_2000-5] Lindekens (2000). "In vivo study of the effect of valpromide and valnoctamide in the pilocarpine rat model of focal epilepsy". Pharmaceutical Research. 17 (11): 1408–13. PMID 11205735. Text " Hilde " ignored (help); Unknown parameter |coauthors= ignored (help); Unknown parameter |month= ignored (help)

[pain-6] Winkler, Ilan (2005). "Efficacy of antiepileptic isomers of valproic acid and valpromide in a rat model of neuropathic pain". British Journal of Pharmacology. PMID 15997234. Unknown parameter |coauthors= ignored (help); Unknown parameter |month= ignored (help)

[kinder_gentler_valproate-7] RH Belmaker, Yuly Bersudsky, Alex Mishory and Beersheva Mental Health Center (2005). "Valnoctamide in Mania". ClinicalTrials.gov. United States National Institutes of Health. Unknown parameter |accessyear= ignored (|access-date= suggested) (help); Unknown parameter |accessdaymonth= ignored (help)

[sleep-8] VALNOCTAMIDE Biam French.

[carbamazepine-9] Pisani F, Fazio A, Artesi C, Oteri G, Spina E, Tomson T, Perucca E. "Impairment of carbamazepine-10, 11-epoxide elimination by valnoctamide, a valpromide isomer, in healthy subjects." British Journal of Clinical Pharmacology. 1992 Jul;34(1):85-7. PMID 1352988

[2s3s-10] Isoherranen, Nina (2003). "Pharmacokinetic-pharmacodynamic relationships of (2S,3S)-valnoctamide and its stereoisomer (2R,3S)-valnoctamide in rodent models of epilepsy". Pharmaceutical Research. 8 (8): 1293–301. PMID 12948028. Unknown parameter |coauthors= ignored (help); Unknown parameter |month= ignored (help)

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