Beta 1- and beta 2-adrenoceptor affinity and stimulatory effects of (S)-pindolol and iodinated (S)-pindolol

The beta 1- and beta 2-adrenoceptor affinity and stimulatory effects of iodinated (S)-pindolol (IPIN) and (S)-pindolol were investigated in vitro using beta-adrenoceptor binding technique and isolated right atrium (rate increase, beta 1) and uterus (relaxation, beta 2) of the rat. IPIN had a higher affinity towards beta-adrenoceptors compared to (S)-pindolol, with some beta 2-adrenoceptor selectivity. In the rat uterus, IPIN produced only marginal stimulatory effects, while (S)-pindolol caused a concentration-dependent relaxation with a maximal effect that was 55% of that generated by isoprenaline. In the right atrium IPIN caused an increase in the atrial rate similar to that caused by (S)-pindolol. The concentration of IPIN required in the right atrium for a half-maximal response (pD2 = 7.81) was markedly greater than that required for occupation of half the beta-adrenoceptor population (pKB = 9.81). The beta 1-selective blocker metoprolol antagonized the effect of (S)-pindolol and IPIN on the atrial rate but a greater concentration of metoprolol (5 X 10(-6) M compared with 5 X 10(-7) M) was required to antagonize the effect of IPIN significantly. It is concluded that iodination of (S)-pindolol increased its affinity and decreased its efficacy towards beta-adrenoceptors.