Valnoctamide
{{Chembox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 477867699
| ImageFile = Valnoctamide.svg
| ImageFile_Ref = {{chemboximage|correct|??}}
| ImageSize = 160
| ImageName = Skeletal formula of valnoctamide
| ImageFile1 = Valnoctamide3D.gif
| PIN = 2-Ethyl-3-methylpentanamide{{Cite web|title=valnoctamide - Compound Summary|url=https://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=20140|work=PubChem Compound|publisher=National Center for Biotechnology Information|access-date=20 February 2012|location=USA|date=26 March 2005|at=Identification and Related Records}}
|Section1={{Chembox Identifiers
| CASNo = 4171-13-5
| CASNo_Ref = {{cascite|changed|??}}
| PubChem = 20140
| PubChem1 = 36689722
| PubChem1_Comment = 2R,3R
| PubChem2 = 10313196
| PubChem2_Comment = 2R,3S
| PubChem3 = 25271745
| PubChem3_Comment = 2S,3R
| PubChem4 = 12015994
| PubChem4_Comment = 2S,3S
| ChemSpiderID = 18974
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID1 = 8488661
| ChemSpiderID1_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID1_Comment = 2R,3S
| UNII = 3O25NRX9YG
| UNII_Ref = {{fdacite|correct|FDA}}
| EINECS = 224-033-7
| KEGG = D02717
| KEGG_Ref = {{keggcite|changed|kegg}}
| MeSHName = valnoctamide
| ChEMBL = 1075733
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| RTECS = YV5950000
| SMILES = CCC(C)C(CC)C(N)=O
| StdInChI = 1S/C8H17NO/c1-4-6(3)7(5-2)8(9)10/h6-7H,4-5H2,1-3H3,(H2,9,10)
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = QRCJOCOSPZMDJY-UHFFFAOYSA-N
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
}}
|Section2={{Chembox Properties
| C=8 | H=17 | N=1 | O=1
| Appearance = White crystals
| LogP = 1.885
}}
|Section6={{Chembox Pharmacology
| ATCCode_prefix = N05
| ATCCode_suffix = CM13
| Bioavail = 94%
| AdminRoutes = {{Unbulleted list|Intravenous|Oral}}
| Metabolism = Hepatic
| HalfLife = 10 hours
}}
|Section7={{Chembox Hazards
| GHSPictograms = {{GHS exclamation mark}}
| GHSSignalWord = WARNING
| HPhrases = {{H-phrases|302}}
| LD50 = 760 mg kg−1 (oral, rat)
}}
|Section8={{Chembox Related
| OtherFunction_label = alkanamides
| OtherFunction = Valpromide
| OtherCompounds = {{Unbulleted list|2-Methylpentane|3-Methylpentane|3-Ethylpentane|2-Ethyl-1-butanol|2-Methylhexane|3-Methylhexane|2-Methylheptane|3-Methylheptane|2-Ethylhexanol|2-Ethylhexanoic acid}}
}}
}}
Valnoctamide (INN, USAN) has been used in France as a sedative-hypnotic since 1964.{{cite journal | first = F. M. | last = Harl |date=March 1964 | language = fr | title = [Clinical Study Of Valnoctamide On 70 Neuropsychiatric Clinic Patients Undergoing Ambulatory Treatment] | journal = La Presse Médicale | volume = 72 | pages = 753–754 | 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 |author2=Meir Bialer |date=August 1989 | title = Structure-pharmacokinetic relationships in a series of valpromide derivatives with antiepileptic activity | journal = Pharmaceutical Research | volume = 6 | issue = 8 | pages = 683–689 | pmid = 2510141 | doi = 10.1023/A:1015934321764| s2cid = 21531402 }}
Indications
In addition to being a sedative, valnoctamide has been investigated for use in epilepsy.{{cite journal | first = S. | last = Mattos Nda |date=May 1969| language = pt | title = [Use of Valnoctamide (nirvanil) in oligophrenic erethics and epileptics] | journal = Hospital (Rio J) | volume = 75 | issue = 5 | pages = 1701–1704 | pmid = 5306499}}{{cite journal | first = H. | last = Lindekens |author2=Ilse Smolders |author3=Ghous M. Khan |author4=Meir Bialer |author5=Guy Ebinger |author6=Yvette Michotte |date=November 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 = 1408–1413 | pmid = 11205735 | doi = 10.1023/A:1007559208599| s2cid = 24229165 }}{{cite journal | last = Rogawski | first= MA |title = Diverse mechanisms of antiepileptic drugs in the development pipeline | journal = Epilepsy Res | year = 2006 | volume = 69 | issue = 3 | pages = 273–294 | pmid = 16621450 | pmc = 1562526 | doi=10.1016/j.eplepsyres.2006.02.004}}
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 |author2=Simcha Blotnik |author3=Jakob Shimshoni |author4=Boris Yagen |author5=Marshall Devor |author6=Meir Bialer |date=September 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 | doi = 10.1038/sj.bjp.0706310 | volume = 146 | pages = 198–208 | issue = 2 | pmc = 1576263}}
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 |author1=RH Belmaker |author2=Yuly Bersudsky |author3=Alex Mishory |author4=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 | access-date = 25 February 2006}}
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.{{cite journal | last1 = Pisani | first1 = F | last2 = Fazio | first2 = A | last3 = Artesi | first3 = C | last4 = Oteri | first4 = G | last5 = Spina | first5 = E | last6 = Tomson | first6 = T | last7 = Perucca | first7 = E | title = Impairment of carbamazepine-10, 11-epoxide elimination by valnoctamide, a valpromide isomer, in healthy subjects | journal = British Journal of Clinical Pharmacology | volume = 34 | issue = 1 | pages = 85–87 | year = 1992 | pmid = 1352988 | pmc = 1381382 | doi=10.1111/j.1365-2125.1992.tb04114.x}}
Chemistry
Valnoctamide is a racemic compound with four stereoisomers,{{cite journal | author = Shimon Barel, Boris Yagen, Volker Schurig, Stephan Sobak, Francesco Pisani, Emilio Perucca and Meir Bialer | url = http://www.nature.com/clpt/journal/v61/n4/full/clpt199736a.html | title = Stereoselective pharmacokinetic analysis of valnoctamide in healthy subjects and in patients with epilepsy | journal = Clinical Pharmacology & Therapeutics | volume = 61 | pages = 442–449 | date = 1997 | issue = 4 | doi = 10.1016/S0009-9236(97)90194-6 | pmid = 9129561 | url-access = subscription }} 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.{{cite journal | first = Nina | last = Isoherranen |author2=H. Steve White |author3=Brian D. Klein |author4=Michael Roeder |author5=José H. Woodhead |author6=Volker Schurig |author7=Boris Yagen |author8=Meir Bialer |date=August 2003 | title = Pharmacokinetic-pharmacodynamic relationships of (2S,3S)-valnoctamide and its stereoisomer (2R,3S)-valnoctamide in rodent models of epilepsy | journal = Pharmaceutical Research | volume = 20 | issue = 8 | pages = 1293–1301 | pmid = 12948028 | doi = 10.1023/A:1025069519218| s2cid = 20755032 }}
Butabarbital can be hydrolyzed to Valnoctamide.{{cite journal|last1=Freifelder|first1=Morris|last2=Geiszler|first2=Adolph O.|last3=Stone|first3=George R.|title=Hydrolysis of 5,5-Disubstituted Barbituric Acids|journal=The Journal of Organic Chemistry|volume=26|issue=1|year=1961|pages=203–206|issn=0022-3263|doi=10.1021/jo01060a048}}
References
{{Reflist|2}}
{{Anticonvulsants}}
{{Hypnotics and sedatives}}
{{Mood stabilizers}}
{{Ion channel modulators}}
{{GABA metabolism and transport modulators}}
{{HDAC inhibitors}}
Category:GABA transaminase inhibitors