Howard J L, Pollard G T, Craft R M, Rohrbach K W
Pharmacol Biochem Behav. 1987 May;27(1):165-9. doi: 10.1016/0091-3057(87)90491-6.
The substituted benzamide metoclopramide has been reported to block the behavioral effects of dopamine agonists, whereas its congener sulpiride potentiates these effects. We injected metoclopramide 2.0, 4.0, or 8.0 mg/kg PO into rats 2 hr before d-amphetamine 1.5 mg/kg IP and measured locomotion for 3 hr. We injected metoclopramide 8.0 mg/kg PO into rats 2 hr before d-amphetamine 1.5, 3.0, or 6.0 mg/kg IP and measured stereotypy for 3 hr. Metoclopramide potentiated the effects of all doses of d-amphetamine on both measures; peak effects occurred in the second or third hr after d-amphetamine injection. Metoclopramide alone tended to reduce behavior. The results suggest that metoclopramide is qualitatively similar to sulpiride in its interaction with d-amphetamine, and that metoclopramide's mechanism of action is not a simple dopaminergic antagonism. Clinicians are advised that metoclopramide, which is presently extensively for gastrointestinal and other disorders, may interact adversely with drugs that affect dopaminergic function.
据报道，取代苯甲酰胺甲氧氯普胺可阻断多巴胺激动剂的行为效应，而其同类物舒必利则会增强这些效应。我们在腹腔注射1.5mg/kg右旋苯丙胺前2小时，经口给大鼠注射2.0、4.0或8.0mg/kg的甲氧氯普胺，并测量3小时内的运动能力。我们在腹腔注射1.5、3.0或6.0mg/kg右旋苯丙胺前2小时，经口给大鼠注射8.0mg/kg的甲氧氯普胺，并测量3小时内的刻板行为。甲氧氯普胺增强了所有剂量右旋苯丙胺对这两种指标的作用；峰值效应出现在注射右旋苯丙胺后的第二或第三小时。单独使用甲氧氯普胺往往会减少行为。结果表明，甲氧氯普胺在与右旋苯丙胺的相互作用上与舒必利在性质上相似，且甲氧氯普胺的作用机制并非简单的多巴胺能拮抗作用。建议临床医生，目前广泛用于治疗胃肠道及其他疾病的甲氧氯普胺，可能会与影响多巴胺能功能的药物产生不良相互作用。
