Lethal synergism between morphine or other narcotic analgesics and propranolol

Interactions of (+/-)-propranolol HCl with various narcotics were determined in albino rats. The 24-h intraperitoneal (i.p.) LD50 of morphine sulfate + saline was 15--16 times greater than for morphine + propranolol in both sexes although morphine was nearly twice as toxic to males as to females. The potency ratios for LD50's with saline vs. with propranolol were: codeine, 1.9, (+/-)-methadone, 6.0; (-)-alpha-acetylmethadol, 2.8 (72 h). The toxicity of levorphanol also was greatly increased with propranolol, but the dose-effect relationship showed non-parallelism vs. levorphanol + saline. Albino mice and mongrel dogs also showed synergism between morphine and propranolol. Mortality after morphine and propranolol was antagonized by naloxone or naltrexone in rats and mice. The potency ratio in rats for morphine + saline vs. morphine + practolol was 3.5. However, the synergism between propranolol and the narcotics probably was unrelated to beta-adrenergic blocking effects of propranolol because of the apparent equivalence of (+)-, (-)- and (+/-)-propranolol in rats for synergism with morphine.