Clinical pharmacology of beta-adrenoceptor blocking drugs possessing partial agonist activity, with special reference to pindolol.
Despite their common property of competitive beta-adrenoceptor blockade, beta-adrenoceptor blocking drugs differ in the presence or absence of several ancillary properties. One of these is partial agonist activity [intrinsic sympathomimetic activity (ISA)]. Drugs of this type are as effective in inhibiting beta-adrenoceptor stimulation as are drugs devoid of ISA, but unlike the latter they produce some stimulation of beta-adrenoceptors. This stimulating activity is sufficient to compensate partly or totally for the loss of resting sympathetic drive resulting from blockade of beta-adrenoceptors. Increases in heart rate during physic and psychic stress, however, are reduced to practically the same extent by all beta-adrenoceptor blocking drugs, whether they possess ISA or not. With pindolol the maximum stimulatory activity is reached at very low doses. Over a dose range wider than that used in clinical practice, the effect of pindolol on resting heart rate is therefore not dependent on the dose but on the heart rate before drug administration. Pindolol is a drug with sufficient ISA to compensate for blockade of sympathetic drive at rest. It therefore does not influence or only slightly reduces normal resting heart rate and cardiac output, and thus does not give rise to reflex increases in total peripheral resistance. During chronic oral treatment of hypertension with pindolol, peripheral resistance is usually reduced.
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D010869:Pindolol / Q000494:pharmacology*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D010869:Pindolol