Modification of the behavioral effects of (+/-)BAY k 8644, cocaine and d-amphetamine by L-type calcium channel blockers in squirrel monkeys.
Modification of the behavioral effects of (+/-)BAY k 8644, cocaine and d-amphetamine by L-type calcium channel blockers in squirrel monkeys.
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L 型钙通道阻滞剂对松鼠猴中 (/-)BAY k 8644、可卡因和 d-安非他明的行为影响的改变。
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发表时间：
1995
期刊：
影响因子：
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通讯作者：
J. Barrett
中科院分区：
文献类型：
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作者：
S. Rosenzweig;J. Barrett
1，4-二氢吡啶-L型钙通道激动剂(+/-)Bay K8644[(+/-)甲基-1，4-二氢-2，6-二甲基-3-nitro-4-(2-trifluoromethylphenyl)-pyridine-5-carboxylate]单胺再摄取抑制剂可卡因和单胺释放剂d-苯丙胺分别与结构不同的L型钙通道阻断剂尼莫地平(1，4-二氢吡啶)、维拉帕米(苯丙胺)、地尔硫卓(苯并噻西平)和氟桂利嗪(二苯基烷胺)预先处理后，分别测定了单胺再摄取抑制剂可卡因和单胺释放剂D-苯丙胺的行为效应。单独给药时，(+/-)Bay k 8644(0.1-0.56 mg/kg)的应答率呈剂量依赖性下降。预先给予尼莫地平(3.0~10 mg/kg)或维拉帕米(1.0~3.0 mg/kg)可使(+/-)Bay k 8644量效曲线右移。相反，预先给予氟桂利嗪(3.0 mg/kg)使(+/-)Bay k 8644量效曲线左移和下移。预先给予地尔硫卓(10-17.8 mg/kg)不改变(+/-)Bay k 8644量效曲线。此外，(+/-)Bay k8644的行为效应具有明显的立体选择性，其中S(-)对映体的效力约为外消旋体的3倍。单独给药时，可卡因(0.1-5.6 mg/kg)和D-苯丙胺(0.1-3.0 mg/kg)的应答率呈剂量依赖性下降。预先给予氟桂利嗪(3.0 mg/kg)可使可卡因和D-苯丙胺量效曲线右移。预先给予尼莫地平(10 mg/kg)、维拉帕米(3 mg/kg)或地尔硫卓(17.8 mg/kg)不能改变可卡因或d-苯丙胺的作用。本研究结果提示，L类钙通道阻滞剂与(+/-)Bay K 8644、可卡因和D-苯丙胺相互作用的不同部位，对(+/-)Bay k 8644的行为效应有不同的影响，提示钙通道阻滞剂可以根据它们与(+/-)Bay k 8644、可卡因和d-苯丙胺相互作用的不同而区分。
Behavioral effects of the 1,4-dihydropyridine L-type calcium channel activator (+/-)BAY k 8644 [(+/-)methyl-1,4-dihydro-2,6-dimethyl-3- nitro-4-(2-trifluoromethylphenyl)-pyridine-5-carboxylate] the monoamine reuptake inhibitor cocaine and the monoamine releaser d-amphetamine were determined alone and after pretreatment with the structurally distinct L-type calcium channel blockers nimodipine (1,4-dihydropyridine), verapamil (phenylakylamine), diltiazem (benzothiazepine) and flunarizine (diphenylalkylamine) in squirrel monkeys responding under a 10-response fixed-ratio schedule of stimulus-shock termination. When administered alone, (+/-)BAY k 8644 (0.1-0.56 mg/kg) produced dose-dependent decreases in rates of responding. Pretreatment with nimodipine (3.0-10 mg/kg) or verapamil (1.0-3.0 mg/kg) produced dose-dependent rightward shifts of the (+/-)BAY k 8644 dose-response curve. In contrast, pretreatment with flunarizine (3.0 mg/kg) produced a leftward and downward shift of the (+/-)BAY k 8644 dose-response curve. Pretreatment with diltiazem (10-17.8 mg/kg) did not modify the (+/-)BAY k 8644 dose-effect curve. In addition, stereoselectivity was evident in the behavioral effects of (+/-)BAY k 8644 with the S(-)-enantiomer being approximately 3-fold more potent than the racemate. When administered alone, cocaine (0.1-5.6 mg/kg) and d-amphetamine (0.1-3.0 mg/kg) produced dose-dependent decreases in rates of responding. Pretreatment with flunarizine (3.0 mg/kg) produced rightward shifts of the cocaine and d-amphetamine dose-response curves. Pretreatment with nimodipine (10 mg/kg), verapamil (3 mg/kg) or diltiazem (17.8 mg/kg) did not modify the effects of cocaine or d-amphetamine. The results of the present study suggest that the behavioral effects of (+/-)BAY k 8644 are differentially modified by L-type calcium channel blockers interacting with different sites on the channel and also suggest that the calcium channel blockers can be distinguished based on their differing interactions with (+/-)BAY k 8644, cocaine and d-amphetamine.