| Central effects of 1,4-butanediol are mediated by GABA(B) receptors via its conversion into gamma-hydroxybutyric acid. | |
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MedLine Citation:
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PMID: 12063087 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The aliphatic alcohol 1,4-butanediol in converted into gamma-hydroxybutyric acid (GHB) via two enzymatic steps: first, it is oxidised by alcohol dehydrogenase in gamma-hydroxybutyraldehyde; second, the latter is transformed, likely by aldehyde dehydrogenase, into GHB. Initially, the present study compared the sedative/hypnotic effect of GHB and 1,4-butanediol, measured as loss of righting reflex. 1,4-Butanediol was more potent than GHB, presumably because of a more rapid penetration of the blood brain barrier. Further alcohol dehydrogenase inhibitors, 4-methylpyrazole and ethanol, totally prevented the sedative/hypnotic effect of 1,4-butanediol; the aldehyde dehydrogenase inhibitor disulfiram partially blocked the sedative/hypnotic effect of 1,4-butanediol. Finally, the sedative/hypnotic effect of 1,4-butanediol was antagonised by the GABA(B) receptor antagonists, SCH 50911 [(2S)(+)-5,5-dimethyl-2-morpholineacetic acid] and CGP 46381 [(3-aminopropyl)(cyclohexylmethyl)phosphinic acid], but not by the putative GHB receptor antagonist NCS-382 (6,7,8,9-tetrahydro-5-hydroxy-5H-benzocyclohept-6-ylideneacetic acid), indicating that it is mediated by GABA(B) but not GHB receptors. Taken together, these results suggest that the sedative/hypnotic effect of 1,4-butanediol is mediated by its conversion in vivo into GHB which, in turn, binds to GABA(B) receptors. Accordingly 1,4-butanediol, unlike GHB, failed to displace [(3)H]GHB and [(3)H]baclofen in brain membranes. |
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Authors:
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Mauro A M Carai; Giancarlo Colombo; Roberta Reali; Salvatore Serra; Ignazia Mocci; M Paola Castelli; Giorgio Cignarella; Gian Luigi Gessa |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: European journal of pharmacology Volume: 441 ISSN: 0014-2999 ISO Abbreviation: Eur. J. Pharmacol. Publication Date: 2002 Apr |
Date Detail:
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Created Date: 2002-06-13 Completed Date: 2002-12-31 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 1254354 Medline TA: Eur J Pharmacol Country: Netherlands |
Other Details:
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Languages: eng Pagination: 157-63 Citation Subset: IM |
Affiliation:
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Neuroscienze S.c.a r.l., Via Palabanda 9, I-09123 Cagliari, Italy. mauro.carai@ns.crs4.it |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Butylene Glycols / metabolism*, pharmacology* Cerebral Cortex / metabolism Dose-Response Relationship, Drug Enzyme Inhibitors / pharmacology Ethanol / pharmacology Hydroxybutyrates / metabolism*, pharmacology* Male Mice Mice, Inbred DBA Rats Rats, Sprague-Dawley Receptors, GABA-B / metabolism* Sleep / drug effects, physiology |
| Chemical | |
Reg. No./Substance:
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0/Butylene Glycols; 0/Enzyme Inhibitors; 0/Hydroxybutyrates; 0/Receptors, GABA-B; 110-63-4/1,4-butanediol; 591-81-1/4-hydroxybutyric acid; 64-17-5/Ethanol |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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