Author/Editor     Jug, Borut
Title     Vpliv fluvoksamina in maprotilina na sproščanje in farmakokinetiko histamina pri podgani in vivo
Translated title     The influence of fluvoxamine and maprotiline on the release and kinetics of histamine in the rat in vivo
Type     članek
Source     Med Razgl
Vol. and No.     Letnik 37, št. 3
Publication year     1998
Volume     str. 293-321
Language     slo
Abstract     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 Iiberation 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 microg/g) or exogenous histmine (10 mocrog/g). Blood samples were taken from the carotid artery at 5 and 15 minutes afler fhe injection of the histamine liberator-for measurements of plasma histamine levels, and at 2 minutes afler the injection of exogenous histamine-for separate determinations of plasma and blood histamine levels. Afler 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 signiflcantly. We suppose that accelerated elimination of histamine is not the resuft 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.
Summary     Antidepresivi prizadenejo farmakokinetiko histamina. Namen naše razsikave je bil natančneje oceniti vpliv različnih odmerkov antidepresivov fluvoksamina in maprotilina na inducirano sproščanje histamina in njegovo nadaljnjo eliminacijo ter opredeliti, ali na eliminacijo vpliva prerazporeditev histamina iz plazme v krvne elemente. Podganam (n = 24) smo vbrizgali po dva enaka odmerka antidepresiva v časovnem razdobju 24 ur. Uro po drugem odmerku antidepresiva smo i. v. vbrizgali sproščevalec histamina - spojino 48/80 (0,05 microg/g) ali eksogeni histamin (10 microg/g). Zatem smo iz skupne karotidne arterije odvzeli vzorce krvi 5 in 15 minut po dodaku sproščevalca, da bi v njih izmerili plazemske ravni histamina, ozirana 2 minuti po vbrizgu histamina. da bi lahko Iočeno analizirali koncentracijo histramina v plazmi in krvi. Koncentracije histamina v vzorcih smo po dvostopenjskem prečiščevanju določili spektrofluorometrično. Oba antideperesiva sta zavrla povišanje plazemske ravni histamina zaradi delovanja sproščevalca. Povečale so se vrednosti hitrostnih konstant eliminacije histamina. Po vbrizgu eksogenega histamina so bile njegove koncentracije v plazmi in krvi podgan z antidepresivom nizje kot pri kontrolnih podganah, ni pa se spremenilo razmerje histamin v plazmi:histamin v krvi. Sklepamo, da antidepresiva zavirata inducirano sproščanje histamina in pospešita njegovo eliminacijo. Domnevamo tudi, da pospešena eliminacijo histamina ni posledica njegovega prerazporejanja iz plazme v krvne elemente, pač pa ji verjetneje botrujeta pospešeno presnavljanje in/ali vezava histamina v druga tkiva. S tem lahko delno pojasnimo nekatere klinične učinke, ki jih imajo antidepresivi na vnetne in alergične procese.
Descriptors     HISTAMINE
HISTAMINE RELEASE
ANTIDEPRESSIVE AGENTS
RATS, WISTAR
FLUVOXAMINE
MAPROTILINE
RECEPTORS, HISTAMINE