The influence of fluvoxamine and maprotiline on the release and kinetics of histamine in the rat in vivo

Antidepressants are known to influence the kinetics of histamine. The purpose of this study was twofold: to determine the influence of various doses of antidepressants fluvoxamine and mapro­tiline on induced histamine liberation and its further elimination and to find out whether histamine elim­ination is influenced by its redistribution from plas­ma to blood. Rats (n = 24) were pre-treated with two doses of antidepressant at an interval of 24 hours. One hour after the administration of the second dose of antidepressants, the rats received histamine liber­ator – compound 48/80 (0.05 pg/g) or exogenous histmine (10 pg/g). Blood samples were taken from the carotid artery at 5 and 15 minutes after the injec­tion of the histamine liberator – for measurements of plasma histamine levels, and at 2 minutes after the injection of exogenous histamine – for separate determinations of plasma and blood histamine lev­els. After a two-step purification procedure, hista­mine levels were measured by spectrofluorometry. Both antidepressants inhibited the rise of plasma histamine because of the effects of compound 48/80. The study animals showed significantly higher val­ues of elimination constants than controls. It is as­sumed that antidepressants inhibit histamine libera­tion and promote its elimination. Rats pre-treated with antidepressants had lower plasma and blood hist­amine levels after exogenous histamine injection than control animals, while their plasma histamine/blood histamine ratio did not change significantly. We suppose that accelerated elimination of hista­mine is not the result of its redistribution from plas­ma to blood and blood elements but is rather the consequence of increased metabolism of histamine and/or its binding in other tissues.