Valnoctamide

Drugbox
IUPAC_name = 2-ethyl-3-methyl-pentanamide

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CAS_number=4171-13-5
ATC_prefix=N05
ATC_suffix=CM13
ATC_supplemental=
PubChem=20140
DrugBank=
C = 8 | H = 17 | N = 1 | O = 1
molecular_weight = 143.227 g/mol
bioavailability= 94%cite journal | first = Abdullah | last = Haj-Yehia | coauthors = Meir Bialer | month = October | year = 1988 | title = Pharmacokinetics of a valpromide isomer, valnoctamide, in dogs. | journal = Journal of Pharmaceutical Science | volume = 77 | issue = 10 | pages = 831–4 | pmid = 3148708 | doi = 10.1002/jps.2600771003]
metabolism = Hepatic
elimination_half-life=10 hours
excretion =
pregnancy_category =
legal_status = Not a controlled substance
routes_of_administration= Oral, intravenous

Valnoctamide (INN, USAN) has been used in France as an sedative-hypnotic since 1964. fr icon cite journal | first = F. M. | last = HARL | month = March | year = 1964 | title = [Clinical Study Of Valnoctamide On 70 Neuropsychiatric Clinic Patients Undergoing Ambulatory Treatment.] | journal = La Presse Médicale | volume = 72 | pages = 753–4. | pmid = 14119722] 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".cite journal | first = Abdullah | last = Haj-Yehia | coauthors = Meir Bialer | month = August | year = 1989 | title = Structure-pharmacokinetic relationships in a series of valpromide derivatives with antiepileptic activity | journal = Pharmaceutical Research | volume = 6 | issue = 8 | pages = 683–9 | pmid = 2510141 | doi = 10.1023/A:1015934321764]

Indications

In addition to being a sedative, valnoctamide has been investigated for use in epilepsy since 1969pt icon cite journal | first = S. | last = Mattos Nda | month = May | year = 1969 | title = [Use of Valnoctamide (nirvanil) in oligophrenic erethics and epileptics.] | journal = Hospital (Rio J) | volume = 75 | issue = 5 | pages = 1701–4 | pmid = 5306499] and was still being investigated in 2000cite journal | last = Lindekens | coauthors = Ilse Smolders, Ghous M. Khan, Meir Bialer, Guy Ebinger, and Yvette Michotte | month = November | year = 2000 | title = In vivo study of the effect of valpromide and valnoctamide in the pilocarpine rat model of focal epilepsy | journal = Pharmaceutical Research | volume = 17 | issue = 11 | pages = 1408–13 | pmid = 11205735 | url = http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&list_uids=11205735&dopt=ExternalLink | doi = 10.1023/A:1007559208599] 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.cite journal | first = Ilan | last = Winkler | coauthors = Simcha Blotnik, Jakob Shimshoni, Boris Yagen, Marshall Devor, and Meir Bialer | month = September | year = 2005 | title = Efficacy of antiepileptic isomers of valproic acid and valpromide in a rat model of neuropathic pain | journal = British Journal of Pharmacology | pmid = 15997234 | url = http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&list_uids=15997234&dopt=ExternalLink | doi = 10.1038/sj.bjp.0706310 | volume = 146 | pages = 198]

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.cite web | author = RH Belmaker, Yuly Bersudsky, Alex Mishory and Beersheva Mental Health Center | year = 2005 | title = Valnoctamide in Mania | url = http://www.clinicaltrials.gov/ct/gui/show/NCT00140179?order=213 | work = ClinicalTrials.gov | publisher = United States National Institutes of Health | accessdaymonth = 25 February | accessyear = 2006]

ide effects

The side effects of valnoctamide are mostly minor and include somnolence [http://www.biam2.org/www/Sub2343.html VALNOCTAMIDE] "Biam" French.] 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.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]

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 ((2"S",3"S")-valnoctamide) was considered to be a good candidate by Isoherranen, et al for an anticonvulsant in August 2003.cite journal | first = Nina | last = Isoherranen | coauthors = H. Steve White, Brian D. Klein, Michael Roeder, José H. Woodhead, Volker Schurig, Boris Yagen, Meir Bialer | month = August | year = 2003
title = Pharmacokinetic-pharmacodynamic relationships of (2S,3S)-valnoctamide and its stereoisomer (2R,3S)-valnoctamide in rodent models of epilepsy | journal = Pharmaceutical Research | volume = 8 | issue = 8 | pages = 1293–301 | pmid = 12948028 | url = http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&list_uids=12948028&dopt=ExternalLink
doi = 10.1023/A:1025069519218]

Notes and references

External links