Effect of propranolol on antinociceptive, tolerance- and dependence-producing properties of morphine in rodents and monkeys.

Since an abstinence syndrome may accompany the injection of opioids in addicts pretreated with propranolol the morphine antagonistic properties of this compound were investigated. Racemic propranolol did not significantly affect the antinociceptive ED50 of morphine in rodents and neither precipitated abstinence in morphine-dependent monkeys nor exacerbated the syndrome in 24 hr withdrawn monkeys. Multiple doses of propranolol did not alter the development of physical dependence on morphine in monkeys. Clinical narcotic antagonism would not be predicted from this profile. Evidence for a possible propranolol-morphine interaction came from studies using the mouse tail flick test. Thus, after 8 injections of propranolol (over 4 days) mice were tolerant to normally effective doses of morphine. Concurrent injections of naloxone antagonised this effect. When propranolol and morphine were administered concurrently the morphine ED50 (on day 5) was twice that of the group receiving morphine alone. Similar results were obtained with d-propranolol; practolol had a neutral effect.