Abstract
Changes in the heart rate response to isoproterenol and cardioaccelerans nerve stimulation were compared before and after i.v. and intraportal vein (pv) doses of dl- or l-bunolol, dl- or l-propranolol and dl-sotalol. Equiactive i.v. doses of the antagonists did not cause equivalent degrees of beta adrenergic receptor blockade after pv administration. dl- and l-Propranolol were less active (P < .05) than the other antagonists after pv administration. Route- and dose-dependent differences were quantitated for individual antagonists by comparing i.v. and pv pA2 and slope values. The reduced activity of pv dl- and l-propranolol was most pronounced after the levo isomer and associated primarily with low cumulative doses. Pretreatment with large pv doses of d-propranolol did not significantly alter the pv response to a low dose of dl-propranolol. SKF 525A pretreatment did not change the relative pv activities of bunolol and propranolol. Carbon tetrachloride pretreatment (hepatotoxic doses): 1) caused a shift in the pv response of propranolol toward that observed after a pv dose of bunolol in normal dogs; 2) had minimal effects on the pv response to bunolol; and 3) prolonged the normally abbreviated pv response of sotalol. It was concluded that the descending order of pharmacologic inactivation after pv administration was: l-propranolol > propranolol >> sotalol > l-bunolol > bunolol. This difference may contribute significantly to l- and dl-bunolol's (and to a lesser degree to sotalol's) favorable oral-to-i.v. dose relationship over propranolol.
Footnotes
- Received August 14, 1972.
- Accepted January 23, 1973.
- © 1973 by The Williams & Wilkins Co.
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