THE DIFFERENTIAL BEHAVIORAL-EFFECTS OF BENZAZEPINE D-1 DOPAMINE AGONISTS WITH VARYING EFFICACIES, CO-ADMINISTERED WITH QUINPIROLE IN PRIMATE AND RODENT MODELS OF PARKINSONS-DISEASE
THE DIFFERENTIAL BEHAVIORAL-EFFECTS OF BENZAZEPINE D-1 DOPAMINE AGONISTS WITH VARYING EFFICACIES, CO-ADMINISTERED WITH QUINPIROLE IN PRIMATE AND RODENT MODELS OF PARKINSONS-DISEASE
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DOI：
10.1007/bf02246103
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发表时间：
1995-02-01
影响因子：
3.4
通讯作者：
MARSDEN, CD
中科院分区：
文献类型：
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作者：
GNANALINGHAM, KK;HUNTER, AJ;MARSDEN, CD
在帕金森病（PD）啮齿动物和灵长类动物模型中，研究了喹吡罗与苯并氮卓类D-1多巴胺（DA）激动剂（具有完全/超大（SKF 80723和SKF 82958）、部分（SKF 38393和SKF 75670）和无效（SKF 83959））联合给药对刺激腺苷酸环化酶（AC）的影响。在内侧前脑束单侧6-羟基多巴胺（6-OHDA）损伤的大鼠中，（7，8-dihydroxy-1-phenyl-2，3，4，5-tetrahydro-1H-3-benzazepine），SKF 75670（3-CH_3类似物）、SKF 80723（6-Br类似物）、SKF 83959（6-Cl，3-CH_3，3 ′-CH_3类似物）和SKF 82958（6-Cl，3-C_3 H_5类似物）强烈增强喹吡罗诱导的对侧环化。在MPTP（1-甲基-4-苯基-1，2，3，6-四氢吡啶）处理的普通绒猴，单独给药quinpirole增加自发活动和逆转运动缺陷。梳理和口腔活动没有改变。SKF 38393和SKF 75670的GO给药抑制了喹吡罗诱导的自发活动和运动残疾的变化。SKF 80723或SKF 82958与喹吡罗的联合治疗对自发活动或运动残疾没有总体影响。相比之下，SKF 83959延长了喹吡罗诱导的运动活动增加的持续时间，并相应降低了运动残疾。GO-给予高剂量SKF 82958，尤其是SKF 83959和SKF 80723，与喹吡罗诱导过度兴奋和癫痫发作。苯并氮杂卓衍生物与喹吡罗共同给药后，口服活性和梳理没有改变。一些苯并氮卓类D-1 DA激动剂延长喹吡罗在MPTP处理的绒猴中的抗帕金森病作用的能力可能表明某些D-1 DA激动剂在PD的临床治疗中的作用。在一般情况下，苯并氮杂卓类与喹吡罗在6-OHDA损伤大鼠，更特别是MPTP处理的绒猴的联合给药的行为反应未能与他们的能力，刺激AC。这些观察结果进一步暗示了与AC无关的D-1 DA受体的行为作用。
The effects of co-administration of quinpirole with benzazepine D-1 dopamine (DA) agonists possessing full/supramaximal (SKF 80723 and SKF 82958), partial (SKF 38393 and SKF 75670) and no efficacies (SKF 83959) in stimulating adenylate cyclase (AC) were investigated in rodent and primate models of Parkinson's disease (PD). In rats with a unilateral 6-hydroxydopamine (6-OHDA) lesion of the medial forebrain bundle, co-administration of SKF 38393 (7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine), SKF 75670 (3-CH3 analogue), SKF 80723 (6-Br analogue), SKF 83959 (6-Cl, 3-CH3, 3'-CH3 analogue) and SKF 82958 (6-Cl, 3-C3H5 analogue) strongly potentiated the contralateral circling induced by quinpirole. In MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) treated common marmosets, administration of quinpirole alone increased locomotor activity and reversed motor deficits. Grooming and oral activity were unaltered. Go-administration of SKF 38393 and SKF 75670 inhibited the quinpirole-induced changes in locomotor activity and motor disability. The combined treatment of SKF 80723 or SKF 82958 with quinpirole had no overall effect on locomotor activity or motor disability. In contrast, SKF 83959 extended the duration of the quinpirole-induced increase in locomotor activity with corresponding decreases in motor disability. Go-administration of high doses of SKF 82958 and more especially SKF 83959 and SKF 80723, with quinpirole induced hyperexcitability and seizures. Oral activity and grooming were unaltered following the co-administration of benzazepine derivatives with quinpirole. The ability of some benzazepine D-1 DA agonists to prolong the antiparkinsonian effects of quinpirole in the MPTP-treated marmoset may indicate a role for certain D-1 DA agonists in the clinical treatment of PD. In general, the behavioural responses to the combined administration of benzazepines with quinpirole in the 6-OHDA lesioned rat and more especially the MPTP-treated marmoset failed to correlate with their ability to stimulate AC. These observations further implicate a behavioural role for D-1 DA receptors not linked to AC.