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Pharmacology of 4‐hydroxypropranolol, a metabolite of propranolol
Author(s) -
FITZGERALD J. D.,
O'DONNELL STELLA R
Publication year - 1971
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.1476-5381.1971.tb07171.x
Subject(s) - propranolol , chronotropic , isoprenaline , heart rate , metabolite , pharmacology , chemistry , active metabolite , endocrinology , medicine , blood pressure , biology , stimulation
Summary1 4‐Hydroxypropranolol, a metabolite produced after oral administration of propranolol, has been shown to be a β‐adrenoceptor blocking drug. It is of similar potency to propranolol in antagonizing the effects of isoprenaline on heart rate and blood pressure in cats and against isoprenaline protection of guinea‐pigs from bronchospasm. It is not cardioselective. 2 In rats depleted of catecholamine 4‐hydroxypropranolol produced an increase in heart rate, suggesting that it has intrinsic sympathomimetic activity. 3 In anaesthetized dogs 4‐hydroxypropranolol produced a decrease in heart rate and dP/dt and an increase in A‐V conduction time at doses within the range 0·09–1·25 mg/kg. These effects are a result of β‐adrenoceptor blockade. In dogs depleted of catecholamines these same doses produced an increase in heart rate and dP/dt and a decrease in A‐V conduction time. These responses were antagonized by propranolol, and were due to the intrinsic sympathomimetic activity of the compound. At higher doses (5·25 and 13·25 mg/kg) a further dose dependent decrease in heart rate and dP/dt and an increase in A‐V conduction time occurred. This trend was also seen in animals depleted of catecholamines. These changes represent membrane stabilizing activity of 4‐hydroxypropranolol. 4 4‐Hydroxypropranolol is a potent β‐adrenoceptor blocking drug with both intrinsic sympathomimetic activity and membrane stabilizing activity.