Effects of α adrenergic blocking agents on narcotic induced analgesia

The influence of a reduction in the action of catecholamines in the nervous system, either by a selective reduction in norepinephrine levels by inhibition of dopamine β hydroxylase or by administration of agents which block catecholamine actions at the receptor site, on morphine induced analgesia was assessed in the rat. Findings indicate that a reduction of norepinephrine in whole brain produces a marked increase in both degree and duration of analgesic response to morphine. The data also suggest that the critical factor in this effect may well be a selective reduction in the effect of norepinephrine at α adrenergic receptors since only the α adrenergic blocker, phenoxybenzamine, but not the β antagonist, propranolol, potentiated morphine induced analgesia. In addition, phenoxybenzamine, but not propranolol, markedly increased the respiratory depressant effect of morphine leading to a substantial number of deaths at doses of each drug several orders of magnitude lower than their individual LD₅₀'s.