Document Detail

Anticonvulsant action in the epileptic gerbil of novel inhibitors of GABA uptake.
MedLine Citation:
PMID:  4007046     Owner:  NLM     Status:  MEDLINE    
Two novel inhibitors of GABA uptake, namely SKF 89976-A (N-[4,4-diphenyl-3-butenyl]-nipecotic acid) and SKF 100330-A (N-[4,4-diphenyl-3-butenyl]-guvacine) were tested for anticonvulsant effects in genetically seizure-prone gerbils. Both compounds proved able to block major (generalized tonic-clonic) seizures initiated in gerbils by air blast stimulation. The respective anticonvulsant ED50s for SKF 100330-A and SKF 89976-A were 1.6 and 4.1 mg/kg i.p., respectively. Comparison with other GABA uptake inhibitors, namely ethyl and methyl esters of (-)- and (+)-nipecotic acid and (+/-)-cis-4-hydroxynipecotic acid, showed that the novel uptake inhibitors were considerably more potent. Similarly, comparison with common antiepileptic drugs demonstrated that SKF 100330-A and SKF 89976-A were more potent than phenobarbital and valproic acid to block seizures in gerbils. Only benzodiazepines surpassed these GABA uptake inhibitors in anticonvulsant potency. Observation of behaviour indicated that the novel compounds exerted no side-effects in anticonvulsant doses. These data indicate that SKF 100330-A and SKF 89976-A deserve interest as potential antiepileptic drugs with a very selective mechanism of action.
W L?scher
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of pharmacology     Volume:  110     ISSN:  0014-2999     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  1985 Mar 
Date Detail:
Created Date:  1985-07-31     Completed Date:  1985-07-31     Revised Date:  2010-03-22    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  103-8     Citation Subset:  IM    
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MeSH Terms
Anticonvulsants / pharmacology*
Depression, Chemical
Epilepsy / drug therapy
Nicotinic Acids / pharmacology*
Nipecotic Acids / pharmacology*
gamma-Aminobutyric Acid / metabolism*
Reg. No./Substance:
0/Anticonvulsants; 0/Nicotinic Acids; 0/Nipecotic Acids; 56-12-2/gamma-Aminobutyric Acid; 85375-85-5/N-(4,4-diphenyl-3-butenyl)nipecotic acid; 85375-88-8/SK&F 100330-A

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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