clozapine and stepholidine

clozapine has been researched along with stepholidine* in 3 studies

Other Studies

3 other study(ies) available for clozapine and stepholidine

ArticleYear
Effects of (-)-stepholidine on NMDA receptors: comparison with haloperidol and clozapine.
    Acta pharmacologica Sinica, 2007, Volume: 28, Issue:7

    To examine whether (-)-stepholidine (SPD) has a direct effect on the N-methyl- D-aspartic acid receptors (NMDAR) containing the NMDA receptor subunits NR2A or NR2B and to compare its effect with those of haloperidol (Hal) and clozapine (Cloz).. NMDAR was transiently expressed in human embryonic kidney 293 (HEK293) cells. Changes in intracellular calcium concentration ([Ca2+]i) induced by NMDAR activation were monitored with Fura-2 ratio imaging techniques.. SPD had no significant effects on either subunit of NMDAR at a concentration of less than 100 micromol/L. Hal selectively inhibited NMDAR containing the NR2B subunit, whereas Cloz inhibited both subunits of NMDAR. Although both Hal and Cloz inhibited NR1a/NR2B receptor-mediated Ca2+ influx, their effects were different. Hal was more potent and had a faster peak effect than Cloz.. Both Hal and Cloz inhibit NMDAR-mediated function, whereas SPD produced only a little inhibition at a high concentration. Based on our other studies, the modulation of SPD on NMDAR function may be via D1 receptor action underlying an indirect mechanism.

    Topics: Animals; Antipsychotic Agents; Berberine; Calcium; Cell Line; Clozapine; Dose-Response Relationship, Drug; Haloperidol; Humans; Protein Subunits; Receptors, Dopamine D1; Receptors, N-Methyl-D-Aspartate

2007
Effects of (-)stepholidine in animal models for schizophrenia.
    Acta pharmacologica Sinica, 2006, Volume: 27, Issue:9

    (-)Stepholidine (SPD) is an active ingredient of the Chinese herb Stephania intermedia, which binds to the dopamine D(1) and D(2) like receptors. Biochemical, electrophysiological and behavioural experiments have provided strong evidence that SPD is both a D(1) and a D(2) 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.. 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.. 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.. 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.

    Topics: Animals; Antipsychotic Agents; Berberine; Clozapine; Dopamine D2 Receptor Antagonists; Haloperidol; Male; Motor Activity; Plants, Medicinal; Rats; Rats, Wistar; Receptors, Dopamine D1; Schizophrenia; Stephania

2006
Effects of l-stepholidine on forebrain Fos expression: comparison with clozapine and haloperidol.
    Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2005, Volume: 30, Issue:2

    l-Stepholidine (SPD) is a tetrahydroprotoberberine alkaloid and a mixed dopamine D1 agonist/D2 antagonist. Preliminary clinical trials suggest that SPD improves both positive and negative symptoms of schizophrenia without producing significant extrapyramidal side effects. Here, we report that SPD mimics the effect of the atypical antipsychotic drug clozapine, preferentially increasing Fos expression in corticolimbic areas. Thus, at 10 mg/kg (i.p.), SPD induced Fos expression in the medial prefrontal cortex (mPFC), nucleus accumbens (NAc), and lateral septal nucleus (LSN) without significantly affecting the dorsolateral striatum (DLSt). At higher doses (20-40 mg/kg), SPD also increased Fos expression in the DLSt. The increase, however, was less pronounced than the increase seen in the NAc. Within the NAc, SPD also induced more Fos expression in the shell than in the core. In all subcortical areas examined, the Fos expression induced by SPD was mimicked by the D2 antagonist sulpiride and reversed by the D2 agonist quinpirole, suggesting that the effect is due to blockade of D2-like receptors by SPD. In the mPFC, however, the effect was not mimicked by sulpride or reversed by quinpirole. It was also not mimicked by the D1 agonist SKF38393 or SKF38393 plus sulpride, and not reversed by the D1 antagonist SCH23390. These results suggest that, in the mPFC, SPD may induce Fos expression through a non-DA mechanism. Whether the mechanism involves an interaction of SPD with other neurotransmitters such as 5-HT and norepinephrine remains to be determined.

    Topics: Animals; Antipsychotic Agents; Berberine; Clozapine; Dopamine Agonists; Dopamine Antagonists; Dopamine D2 Receptor Antagonists; Haloperidol; Immunohistochemistry; Neostriatum; Nucleus Accumbens; Prosencephalon; Proto-Oncogene Proteins c-fos; Rats; Rats, Sprague-Dawley; Receptors, Dopamine D1; Receptors, Dopamine D2; Septal Nuclei

2005