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Stereoselectivity of S- and R-sulpiride for pre- and postsynaptic dopamine receptors in the canine kidney

AS Bass and NW Robie

The stereoselectivity of S (S)- and R (R)-sulpiride for the pre- (prereceptor) and post (postreceptor) synaptic dopamine receptors has been examined in various tissues. In the present study, the effects of S and R on the pre- and postreceptor in the canine kidney were investigated. The left renal artery of pentobarbital-anesthetized dogs was exposed and mean arterial pressure and renal blood flow were monitored. Vasoconstrictor stimuli [nerve stimulation: 1-8 Hz, 2 msec, 10-20 V, 5 sec; norepinephrine: 0.25-1.0 micrograms i.a.] were produced before and during graded doses of dopamine (DA: 0.3-2.4 micrograms/kg/min i.a.) administration. After a 15-minute recovery period, vasoconstrictor stimuli were repeated before and during the reinfusion of DA at the 2.4-micrograms/kg/min dose. While continuing DA, S or R (0.06-15.6 micrograms/kg/min) was administered and vasoconstrictor stimuli were repeated. DA antagonized the response to nerve stimulation but not norepinephrine (P less than .05). This effect of DA was antagonized by S at a dose of 0.12 micrograms/kg/min but not R. S and R alone did not affect the response to nerve stimulation. In dogs pretreated with phenoxybenzamine (5 mg/kg i.a.), DA produced a decrease in renal vascular resistance (P less than .05) and a dose of 15.6 micrograms/kg/min of either S or R was required to block this effect of DA. Therefore, S is 130 times more stereoselective for the prereceptor, whereas S and R are equipotent at the postreceptor in the canine kidney.

Volume 229, Issue 1, pp. 67-71, 04/01/1984
Copyright © 1984 by American Society for Pharmacology and Experimental Therapeutics




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Copyright © 1984 by the American Society for Pharmacology and Experimental Therapeutics.