Suzuki T, Masukawa Y, Misawa M
Department of Applied Pharmacology, School of Pharmacy, Hoshi University, Tokyo, Japan.
Psychopharmacology (Berl). 1990;102(4):438-42. doi: 10.1007/BF02247122.
Drug interactions in reinforcin effects of over-the-counter cough syrups were investigated by utilizing place preference conditioning in rats. Dihydrocodeine (2 mg/kg, IP) induced a small, non-significant place preference. On the other hand, concurrent dosing of dihydrocodeine (2 mg/kg, IP) and a mixture (SC) of methylephedrine (4 mg/kg), caffeine (4 mg/kg) and chlorpheniramine (0.8 mg/kg) produced a significant place preference, the mean conditioning score in this group being about 3 times higher than that in the dihydrocodeine alone group. The potentiation of dihydrocodeine-conditioned place preference was observed by combination with chlorpheniramine (0.8 mg/kg, SC) alone as well as with the mixture, but neither with methylephedrine (4 mg/kg, SC) nor with caffeine (4 mg/kg, SC). Chronic infusion of the dopamine D1 receptor antagonist SCH23390 (1.0 mg/kg/day, SC) during conditioning abolished the appetitive effects of dihydrocodeine combined with chlorpheniramine. In conclusion, it is suggested that the potentiation of appetitive effects of dihydrocodeine is mostly due to chlorpheniramine among three ingredients in the cough syrups, and that the dopaminergic system, especially D1 receptor, may play an important role in the potentiation effect of chlorpheniramine on the reinforcing effects of dihydrocodeine.
通过在大鼠中利用位置偏爱条件反射来研究非处方止咳糖浆增强作用中的药物相互作用。二氢可待因（2毫克/千克，腹腔注射）诱导出轻微的、不显著的位置偏爱。另一方面，二氢可待因（2毫克/千克，腹腔注射）与甲基麻黄碱（4毫克/千克）、咖啡因（4毫克/千克）和氯苯那敏（0.8毫克/千克）的混合物（皮下注射）同时给药产生了显著的位置偏爱，该组的平均条件反射得分比仅使用二氢可待因的组高出约3倍。单独与氯苯那敏（0.8毫克/千克，皮下注射）以及与该混合物联合使用时，观察到二氢可待因条件性位置偏爱的增强，但与甲基麻黄碱（4毫克/千克，皮下注射）或咖啡因（4毫克/千克，皮下注射）联合使用时未观察到增强。在条件反射过程中慢性输注多巴胺D1受体拮抗剂SCH23390（1.0毫克/千克/天，皮下注射）消除了二氢可待因与氯苯那敏联合使用的奖赏效应。总之，提示在止咳糖浆的三种成分中，二氢可待因奖赏效应的增强主要归因于氯苯那敏，并且多巴胺能系统，尤其是D1受体，可能在氯苯那敏对二氢可待因强化作用的增强效应中起重要作用。
