β1‐ and β2‐Adrenoceptor Affinity and Stimulatory Effects of (S)‐Pindolol and Iodinated (S)‐Pindolol

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Abstract
The .beta.1- and .beta.2-adrenoceptor affinity and stimulatory effects of iodinted (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 (pKa= 9.81). The .beta.-selective blocker metoprolol antagonized the effect of (S)-pindolol and IPIN on the atrial rate but a greater concentration of metoprolol (5 .times. 10-6 M compared with 5 .times. 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.

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