Neuropharmacological effects of isomers of hexachlorocyclohexane—3. An account of the convulsant activity of the γ-isomer in rats

A study was made of the somatomotor responses of rats to y-hexachlorocyclohexane, the insecticide lindane, with a view to assessing its properties as a convulsant in mammals. The drug was known to successively elicit a (myo-)clonic and a (myo-)clonic-tonic seizure on slow intravenous infusion as does pentylenetetrazol. The correspondence with pentylenetetrazol is now shown to include, apart from premonitory signs and a certain form of postictal state (1) the ontogenetic development of the two different types of seizure; (2) the antagonistic action of trimethadione and of the α-isomer of hexachlorocyclohexane; (3) a facilitatory action of reserpine. Further, an identical series of locomotor behaviours has been found to be elicited by γ-hexachlorocyclohexane and pentylenetetrazol upon injection into basal strata of allo- and neocortex overlying the tectum or into the superior colliculus none of which, however, constitutes a significant early part of the sequence of effects seen after systemic administration. The implications of this discrepancy are considered with reference to evidence which would seem to indicate that the response obtained by topical application into the tectum might be initiated through interference with GABAergic neurotransmission. Consideration is also given to the pharmacokinetic properties of the insecticide which bear on onset of action and apparent potency in relation to pentylenetetrazol. It is concluded that γ-hexachlorocyclohexane exerts its somatomotor effects in a manner akin to pentylenetetrazol with respect to target sites and modes of excitation.