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Exp Anim. 2018 May 10;67(2):163-173. doi: 10.1538/expanim.17-0091. Epub 2017 Dec 8.

Investigation of the synergistic effects of haloperidol combined with Calculus Bovis Sativus in treating MK-801-induced schizophrenia in rats.

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Department of Pharmacy, Tongji Hospital, Tongji Medical School, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, P.R. China.
Department of Pharmacy, Changzhou Tumor Hospital, 68 Honghe Road, Xinbei District, Changzhou 213032, P.R. China.


Clinical studies that focused on treating schizophrenia showed that Calculus Bovis Sativus (CBS), a substitute of Calculus Bovis, when used in combination with haloperidol could significantly lower the dosage of haloperidol compared with treatment with haloperidol alone, whereas efficacy was maintained. The aim of this study was to investigate the synergetic anti-schizophrenia effects in rats using CBS in combination with haloperidol. An open field test was conducted to verify the pharmacodynamic effects of a combination treatment of CBS and haloperidol on MK-801-induced schizophrenic rats. Rat plasma concentrations of intragastric haloperidol and intravenous haloperidol were determined after oral administration of a single dose or 1-week of pretreatment with CBS (50 mg/kg). The pharmacodynamic data showed a significant decrease in locomotor activity and an increase in the percentage of the central distance when haloperidol was concomitantly administered with CBS compared with haloperidol administration alone. The AUC0-∞ and Cmax of haloperidol in the orally coadministered groups were significantly higher compared with the oral treatment with haloperidol alone. In conclusion, oral coadministration of CBS with haloperidol resulted in a synergistic effect in rats. The enhanced oral bioavailability of haloperidol when combined with CBS might be attributed to the interaction between them.


Calculus Bovis Sativus; haloperidol; pharmacodynamics; pharmacokinetics; synergism

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