REDUCTION OF GAMMA-AMINOBUTYRIC ACID (GABA) MEDIATED TRANSMISSION BY A CONVULSANT BENZODIAZEPINE

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  • 1 January 1979
    • journal article
    • research article
    • Vol. 211  (2) , 290-295
Abstract
In contrast to other benzodiazepines, Ro 5-3663 produces convulsions in mice. The CD50 [median convulsant dose] of 7.0 mg/kg i.v. falls between that of picrotoxin and pentylenetetrazol. An electrophysiological study was made of the effects of this convulsant benzodiazepine on spinal reflexes and on ganglionic depolarization evoked by GABA. In the unanesthetized spinal cat, Ro 5-3663 [1,3-dihydro-5-methyl-2H-1,4-benzodiazepine-2-one] (15 mg/kg i.v.) depressed the dorsal root potentials and abolished the dorsal root reflexes evoked by muscle and cutaneous afferent inputs. The monosynaptic reflex was typically depressed, whereas polysynaptic potentials were enhanced. Diazepam reversed the depression of the dorsal root reflex and dorsal root potential produced by the convulsant benzodiazepine and reduced the enhancement of the polysynaptic potential. Presynaptic inhibition was attenuated by the convulsant, whereas strychnine-sensitive postsynaptic inhibition was slightly potentiated. Ro 5-3663 reduced the amplitude and duration of the GABA-evoked negative surface potential recorded from the superio cervical ganglion. The convulsant benzodiazepine apparently acts in an opposite manner to the depressant benzodiazepines and support the hypothesis that these 2 types of compounds act through a modulation of GABAergic mechanisms.