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  • Title: Reduction of gamma-aminobutyric acid (GABA)-mediated transmission by a convulsant benzodiazepine.
    Author: Schlosser W, Franco S.
    Journal: J Pharmacol Exp Ther; 1979 Nov; 211(2):290-5. PubMed ID: 501563.
    Abstract:
    In contrast to other benzodiazepine, Ro 5-3663 produces convulsions in mice. The CD50 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 gamma-aminobutyric acid (GABA). In the unanesthetized spinal cat, Ro 5-3663 (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 superior cervical ganglion. The results indicate that the convulsant benzodiazepine acts in an opposite manner to the depressant benzodiazepines and support the hypothesis that these two types of compounds act through a modulation of GABAergic mechanisms.
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