Acta Pharmacologica Sinica 2006 September; 27 (9): 1111-1118; doi: 10.1111/j.1745-7254.2006.00365.x

Aim: (-)Stepholidine (SPD) is an active ingredient of the Chinese herb Stephania intermedia, which binds to the dopamine D₁ and D₂ like receptors. Biochemical, electrophysiological and behavioural experiments have provided strong evidence that SPD is both a D₁ and a D₂ antagonist, which could make SPD a unique antipsychotic drug. The present study aimed to investigate the antipsychotic properties of SPD in two animal models for schizophrenia.

Methods: The effects of SPD, clozapine and haloperidol in increasing forelimb and hindlimb retraction time in the paw test and in reversing the apomorphine and MK801-induced disruption of prepulse inhibition was investigated.

Results: In the paw test, clozapine and SPD increased the hindlimb retraction time, with only a marginal effect on the forelimb retraction time, whereas haloperidol potently increased both. In the prepulse inhibition paradigm, all three drugs reverse the apomorphine-induced disruption in prepulse inhibition, while none of the drugs could reverse the MK801-induced disruption. SPD even slightly, but significantly, potentiated the effects of MK801.

Conclusion: The data show that SPD showed antipsychotic-like effects in both the prepulse inhibition paradigm and in the paw test. Moreover, the results of the paw test suggest that SPD has an atypical character with a relatively small potency to induce extrapyramidal side effects.

Keywords: acoustic startle response; antipsychotics; apomorphine; dopamine D₁ receptor; dopa-mine D₂ receptor; MK801; paw test; prepulse inhibition; clozapine; haloperidol