DOPAMINE D-1 RECEPTOR AGONISTS DISPLAY A DIFFERENT INTRINSIC ACTIVITYIN RAT, MONKEY AND HUMAN ASTROCYTES

Measuring dopamine D-1 receptor stimulated cyclic AMP production in cu ltured astrocytes from rat, monkey and human brain, we demonstrate tha t the 'classical' drug SKF 38393 (7,8-dihydroxy-1-phenyl-2,3,4,5-tetra hydro-1 H-3-benzazepine) is a partial agonist with particularly low in trinsic activity in primates. Furthermore, its analogue SKF 81297 chlo ro-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1 H-3-benzazepine) is sho wn to be a full agonist in rats but a partial, albeit more efficacious , agonist in primates, whereas the benzopyran A 68930 S)-1-aminomethyl -5,6-dihydroxy-3-phenyl-isochroman HCl) displays full efficacy in both species. The data suggest that cultured astrocytes provide a good mod el to study species differences in the pharmacological characteristics of dopamine D-1 receptor agonists and indicate that SKF 38393 is not suited to study dopamine D-1 receptor function in primates.