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In vitro inhibitory effects of narcotic analgesics and other psychotropic drugs on the active uptake of norepinephrine in mouse brain tissue.

F. Carmichael,Y. Israel

Published 1973 in Journal of Pharmacology and Experimental Therapeutics

ABSTRACT

The effect of several narcotic analgesics and other psychotropic compounds On the uptake of 3 H-norepinephrine by mouse brain slices or synaptosomes was studied. Codeine, hydromorphone, levorphanol, meperidine, methadone, morphine and naloxone inhibited the uptake of norepinephrine. However, there was no correlation between their inhibitory potency and their analgesic potency. Naloxone failed to antagonize the inhibitory effect of morphine. No difference in inhibitory potency of the d - and l -isomers of methadone on the uptake of norepinephrine was found. Chronic administration of morphine in a schedule which rendered the animals physically dependent on morphine had no effect on the uptake of norepinephrine by brain slices or synaptosomes. The above findings suggest that an inhibition of the uptake of norepinephrine is not involved in the in vivo effects of morphine. Several other psychotropic drugs such as desipramine, chlorpromazine and benztropine were found to be potent inhibitors of the uptake of norepinephrine in vitro . A highly significant correlation was observed between the inhibition of uptake of norepinephrine by all the compounds studied and their lipid solubility, expressed as octanol/water partition coefficients. The minimal inhibitory potency of other psychotropic compounds on the active uptake of norepinephrine can be predicted from their lipid solubility.

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