The effects of co-administration of
quinpirole with benzazepine D1
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. Co-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. Co-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 D1 DA agonists to prolong the antiparkinsonian effects of
quinpirole in the
MPTP-treated marmoset may indicate a role for certain D1 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 D1 DA receptors not linked to AC.