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.
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D005260:Female; D006325:Heart Atria / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008790:Metoprolol / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D010869:Pindolol / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000378:metabolism; D014599:Uterus / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; C026777:ICI 118551; C029247:3-iodopindolol; D010869:Pindolol; D008790:Metoprolol