Abstract |
The behavioral profile of the optical isomers of 1-methyl-5-phenyl-5-propylbarbituric acid ( MPPB) and their interaction with the convulsant binding site at the GABA receptor complex were investigated. R(-)- MPPB produced dose-related loss of righting reflex, whereas S(+) MPPB produced convulsions in a dose-dependent manner. Subconvulsive doses of S(+) MPPB were proconvulsant with a subeffective dose of picrotoxin. S(+) MPPB-induced seizures were blocked by R(-) MPPB and pentobarbital. In contrast, S(+) MPPB did not block the loss of righting reflex produced by R(-) MPPB or pentobarbital. S(+) MPPB inhibited the binding of [35S] t-butylbicyclophosphorothionate ( TBPS), a ligand that binds to the picrotoxin site on the oligomeric GABA receptor complex, to rat brain membranes competitively, whereas R(-) MPPB inhibited it noncompetitively. Thus, the optical isomer of MPPB, which have opposite pharmacological effects, interact differently with the convulsant ( TBPS) site at the GABA receptor complex. These results suggest that the convulsant S(+) MPPB and the depressant R(-) MPPB may produce their behavioral effects by acting via convulsant and anticonvulsant sites, respectively, at the GABA receptor complex.
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Authors | M K Ticku, S K Rastogi, R Thyagarajan |
Journal | European journal of pharmacology
(Eur J Pharmacol)
Vol. 112
Issue 1
Pg. 1-9
(May 28 1985)
ISSN: 0014-2999 [Print] Netherlands |
PMID | 2990963
(Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Anticonvulsants
- Convulsants
- Receptors, GABA-A
- Picrotoxin
- 1-methyl-5-phenyl-5-propylbarbituric acid
- Pentobarbital
- Phenobarbital
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Topics |
- Animals
- Anticonvulsants
- Brain
(metabolism)
- Convulsants
- In Vitro Techniques
- Kinetics
- Male
- Pentobarbital
(pharmacology)
- Phenobarbital
(analogs & derivatives, metabolism, pharmacology)
- Picrotoxin
(pharmacology)
- Postural Balance
(drug effects)
- Rats
- Rats, Inbred Strains
- Receptors, GABA-A
(drug effects, metabolism)
- Stereoisomerism
- Time Factors
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