Influence of caffeine and midazolam on gamma-aminobutyric acid-evoked responses in the frog spinal cord.
The recently reported potentiation of gamma-aminobutyric acid (GABA) evoked depolarizations by caffeine in the frog spinal cord might involve an interaction with GABA-linked benzodiazepine receptors. This possibility was investigated using a new potent benzodiazepine, midazolam, and a benzodiazepine antagonist, Ro 147437. Caffeine or midazolam enhanced the amplitude of submaximal GABA responses by about 50%; when equieffective enhancing doses of these compounds were simultaneously applied, GABA depolarizations were usually depressed below control levels. It was however possible to detect a narrow range of concentrations of midazolam which had an additive effect to the enhancement by caffeine. Ro 147437 did not block caffeine-induced potentiations of GABA responses. It is suggested that caffeine and benzodiazepines have distinct modes of action in modulating GABA-induced depolarizations in the in vitro spinal cord of the frog.
D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology*; D002110:Caffeine / Q000494:pharmacology*; D004357:Drug Synergism; D004594:Electrophysiology; D066298:In Vitro Techniques; D008874:Midazolam; D011896:Rana temporaria; D011956:Receptors, Cell Surface / Q000378:metabolism; D011963:Receptors, GABA-A; D013116:Spinal Cord / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; D001569:Benzodiazepines; D002110:Caffeine; D005680:gamma-Aminobutyric Acid; D008874:Midazolam