Effect of isofloxythepin, a novel neuroleptic, on hippocampal stimulation-induced wet-dog shaking in the rat.

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(±)isofloxythepin (0.32-3.2 mg/kg, i.p.) significantly inhibited in a dose-dependent manner wet-dog shaking (WDS) induced by electrical stimulation of the rat hippocampus. In addition, both optical isomers of isofloxythepin inhibited WDS, with the (-)-isomer being almost 3 times more potent than the (+)-isomer. Other neuroleptics such as haloperidol, chlorpromazine, zotepine and sulpiride also reduced significantly the number of WDS. The inhibitory potency of haloperidol was comparable to that of (±)isofloxythepin, which was approximately 3 times more potent than that of chlorpromazine or zotepine. Sulpiride suppressed significantly WDS only at the high dose of 100 mg/kg. None of the drugs affected hippocampal afterdischarge. Inhibition of WDS produced by (±)isofloxythepin or haloperidol was antagonized by pretreatment with a dopamine receptor agonist, lisuride. The present results indicate that isofloxythepin shares with other neuroleptics an inhibitory effect on WDS; dopaminergic blocking action appears to be important in the inhibition of WDS induced by hippocampal stimulation.
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