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Mode of action of (‐)‐pindolol on feline and human myocardium
Author(s) -
Kaumann Alberto J.,
Lobnig Brigitte M.
Publication year - 1986
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1986.tb11137.x
Subject(s) - pindolol , chronotropic , inotrope , kitten , medicine , endocrinology , ventricle , chemistry , methysergide , propranolol , atrium (architecture) , antagonist , receptor , heart rate , blood pressure , cats , atrial fibrillation
1 (‐)‐Pindolol antagonized competitively and to a similar extent the positive inotropic effects of both (‐)‐noradrenaline and (‐)‐adrenaline in human ventricular preparations. An equilibrium dissociation constant K D (‐log mol 1 −1 = pK D ) of 9.2–9.3 was estimated regardless of disease present or agonist used. 2 (‐)‐Pindolol antagonized competitively the positive inotropic effects of (‐)‐adrenaline more than those of (‐)‐noradrenaline in human atrial preparations. pK D values of (‐)‐pindolol were 9.6 against (‐)‐adrenaline and 9.1 against (‐)‐noradrenaline. The results are consistent with a moderate selectivity of (‐)‐pindolol for β 2 ‐ compared to β 1 ‐adrenoceptors in human atrium. 3 (‐)‐Pindolol competed with [ 3 H]‐(‐)‐bupranolol with a pK D of 9.4 for β‐adrenoceptors of human ventricle. 4 Positive inotropic effects of (‐)‐pindolol were not detected on human atrium or ventricle in a concentration range of 1–1000 nmol 1 −1 . 5 The affinity of (‐)‐pindolol estimated for human myocardial β‐adrenoceptors, its moderate β 2 ‐selectivity and its lack of intrinsic activity for contractile force agreed with similar characteristics in other species. 6 (‐)‐Pindolol caused marked positive chronotropic effects in kitten right atria with an intrinsic activity of 0.5 with respect to catecholamines. On kitten left atria it caused only weak positive inotropic effects with an intrinsic activity of 0.1. (‐)‐Pindolol (0.6–6000 nmol −1 ) did not cause positive inotropic effects in kitten papillary muscle. 7 The concentration‐effect curve for (‐)‐pindolol on kitten right and left atria was biphasic. Its positive chronotropic and inotropic effects were not blocked by methysergide, suggesting that 5‐hydroxytryptamine (5‐HT)‐receptors were not involved. Low concentrations of antagonists selective for β 1 ‐ and β 2 ‐adrenoceptors blocked the high sensitivity component but not the low sensitivity component of the positive chronotropic and inotropic effects. 8 The biphasic nature of the positive chronotropic effects of (‐)‐pindolol in kitten agreed with previous observations made on guinea‐pig right atria and support the concept that 3 receptors in the sinoatrial pacemaker contribute to these chronotropic effects: β 1 β 2 and a low‐affinity receptor for (‐)‐pindolol which is neither β 1 nor β 2 . The partial agonistic activity of (‐)‐pindolol in the heart appears to be mainly (kitten) or completely (man) restricted to the sinoatrial pacemaker.