valnoctamide

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/07/21 02:20:18」(JST)

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Valnoctamide
IUPAC name 2-Ethyl-3-methylpentanamide
Identifiers
CAS number	4171-13-5 N
PubChem	20140, 36689722 2R,3R, 10313196 2R,3S, 25271745 2S,3R, 12015994 2S,3S
ChemSpider	18974 Y, 8488661 2R,3S Y
UNII	3O25NRX9YG Y
EC number	224-033-7
KEGG	D02717 N
MeSH	valnoctamide
ChEMBL	CHEMBL1075733 Y
RTECS number	YV5950000
ATC code	N05CM13
Jmol-3D images	Image 1 Image 2
SMILES CCC(C)C(CC)c(:[nH2]):[o] CCC(C)C(CC)C(N)=O
InChI InChI=1S/C8H17NO/c1-4-6(3)7(5-2)8(9)10/h6-7H,4-5H2,1-3H3,(H2,9,10) Y Key: QRCJOCOSPZMDJY-UHFFFAOYSA-N Y
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
GHS signal word	WARNING
GHS hazard statements	H302
EU classification	Xn
R-phrases	R22
LD50	760 mg kg−1 (oral, rat)
Related compounds
Related alkanamides	Valpromide
Related compounds	2-Methylpentane 3-Methylpentane 3-Ethylpentane 2-Ethyl-1-butanol 2-Methylhexane 3-Methylhexane 2-Methylheptane 3-Methylheptane 2-Ethylhexanol 2-Ethylhexanoic acid
Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
N (verify) (what is: Y/N?)
Infobox references

Valnoctamide (INN, USAN) has been used in France as a sedative-hypnotic since 1964. 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.

Indications

In addition to being a sedative, valnoctamide has been investigated for use in epilepsy since 1969 and was still being investigated in 2000 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.

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.

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.

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 2003.

References

UpToDate Contents

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• 1. 妊娠女性における双極性障害：躁病および軽躁の治療 bipolar disorder in pregnant women treatment of mania and hypomania

English Journal

• Valnoctamide, which reduces rat brain arachidonic acid turnover, is a potential non-teratogenic valproate substitute to treat bipolar disorder.

• Modi HR1, Ma K1, Chang L1, Chen M1, Rapoport SI2.
• Psychiatry research.Psychiatry Res.2017 Aug;254:279-283. doi: 10.1016/j.psychres.2017.04.048. Epub 2017 Apr 26.
• PMID 28500975

• Valnoctamide Inhibits Cytomegalovirus Infection in Developing Brain and Attenuates Neurobehavioral Dysfunctions and Brain Abnormalities.

• Ornaghi S1,2,3, Hsieh LS1, Bordey A1,4, Vergani P5, Paidas MJ2, van den Pol AN6.
• The Journal of neuroscience : the official journal of the Society for Neuroscience.J Neurosci.2017 Jul 19;37(29):6877-6893. doi: 10.1523/JNEUROSCI.0970-17.2017. Epub 2017 Jun 19.
• PMID 28630251

• A randomized, double-blind, placebo- and risperidone-controlled study on valnoctamide for acute mania.

• Weiser M1,2, Levi L1, Levine SZ3, Bialer M4, Shekh-Ahmad T4, Matei V5, Tiugan A6, Cirjaliu D7, Sava C8, Sinita E9, Zamora D10, Davis JM11.
• Bipolar disorders.Bipolar Disord.2017 Jun;19(4):285-294. doi: 10.1111/bdi.12506. Epub 2017 Jun 12.
• PMID 28605109

Japanese Journal

• In vivo study of the effect of valpromide and valnoctamide in the pilocarpine rat model for focal epilepsy

• LINDEKENS H.
• Pharm Res 17, 1408-1413, 2000
• NAID 80012272096

• 高分子と医薬品との相互作用-5-橋かけ高分子電解質による錠剤の崩壊機構

• 平田 五一
• 薬学雑誌 90(2), 114-119, 1970-02
• … In order to examine the application of tablets of polyelectrolytes, crosslinked with divinylbenzene to a low degree, to disintegration agent, two kinds of materials with different degree of swelling, crosslinked polyacrylic acid and crosslinked polymethacrylic acid, were selected and their disintegration behavior was examined from the point of swelling and fluidity, in the disintegration of valnoctamide tablet, which is extremely difficult to disintegrate, in water, and in the presence of inorganic salts or dl-methylephedrine hydrochloride. …
• NAID 110003654334

• 高分子と医薬品との相互作用(第5報) : 橋かけ高分子電解質による錠剤の崩壊機構

• 平田 五一
• 藥學雜誌 90(2), 114-119, 1970
• … In order to examine the application of tablets of polyelectrolytes, crosslinked with divinylbenzene to a low degree, to disintegration agent, two kinds of materials with different degree of swelling, crosslinked polyacrylic acid and crosslinked polymethacrylic acid, were selected and their disintegration behavior was examined from the point of swelling and fluidity, in the disintegration of valnoctamide tablet, which is extremely difficult to disintegrate, in water, and in the presence of inorganic salts or dl-methylephedrine hydrochloride. …
• NAID 130007286499

Related Links

• Valnoctamide - Wikipedia, the free encyclopedia

Valnoctamide (INN, USAN) has been used in France as a sedative-hypnotic since 1964. It is a structural isomer of valpromide, a valproic acid prodrug; unlike valpromide, however, valnoctamide is not transformed into its homologous acid, ...