Selective inhibition of central sympathetic neurons by morphine and its reversal by naloxone.

Recent investigations clarifying the monoaminergic influences on sympathetic preganglionic neurons in the cat have allowed a direct assessment of the effects of narcotic analgesics and antagonists on central transmission. Intravenous morphine, methadone, meperidine or codeine produced an immediate and sustained depression of discharges evoked from these spinal sympathetic neurons. The potency rations for production of similar degrees of depression by these four agents compared favorably to the potency ratios reported for equianalgesic doses. The depression appeared to be specific in that it was rapidly reversed by very low doses of naloxone or nalorphine and that a non-analgesic stereoisomer related to these drugs produced qualitatively different effects on the sympathetic preganglionic neurons. The depression of these neurons offers an adequate and sufficient mechanism to account for the centrally mediated vasodepressor effect produced by morphine and other narcotic analgesics. The pharmacological characterization of the morphine and naloxone actions strongly suggests that morphine functions as a 5-HT agonist in this system, while naloxone can both block 5-HT receptors and also stimulate these spinal neurons. The significance of these findings relative to other acute and chronic effects of the narcotic analgesics are discussed.