Effects of the histamine H2-receptor agonists dimaprit and 4-methylhistamine on the central noradrenaline and serotonin system.
Effects of dimaprit and 4-methylhistamine, two histamine H2-receptor agonists, on noradrenaline and serotonin systems in the rat brain were investigated. Administration of dimaprit into the lateral brain ventricle produced 30% decrease in hypothalamal noradrenaline. 2 h after administration of dimaprit the level of 3-methoxy-4-hydroxyphenylglycol was increased by 50%. 4-Methylhistamine and histamine produced qualitatively the same effects as dimaprit. Dimaprit and 4-methylhistamine increased locomotor activity in tranylcypromine-treated rats. The hyperkinetic action of both drugs was prevented by phenoxybenzamine. Dimaprit had negligible effect on the serotonin system while 4-methylhistamine and histamine decreased serotonin and simultaneously increased 5-hydroxyindolcacetic acid. 4-Methylhistamine and histamine, but not dimaprit, evoked head-twitches in tranylcypromine-treated rats. It is concluded that dimaprit and 4-methylhistamine act similarly on the noradrenaline system, probably releasing noradrenaline, but having different effects on the serotonin system. 4-Methylhistamine (and histamine) probably releases serotonin from rat hypothalamus while dimaprit does not. The results are discussed in relation to a possible interaction of histamine with both noradrenaline and serotonin systems in the rat brain.
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D017259:Dimaprit; D005260:Female; D006632:Histamine / Q000494:pharmacology; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008734:Methoxyhydroxyphenylglycol / Q000378:metabolism; D008761:Methylhistamines / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D011968:Receptors, Histamine / Q000187:drug effects*; D011970:Receptors, Histamine H2 / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism / Q000502:physiology*; D013890:Thiourea / Q000494:pharmacology*; D014191:Tranylcypromine / Q000494:pharmacology
D008761:Methylhistamines; D011968:Receptors, Histamine; D011970:Receptors, Histamine H2; D012701:Serotonin; D014191:Tranylcypromine; D008734:Methoxyhydroxyphenylglycol; D006897:Hydroxyindoleacetic Acid; C025566:4-methylhistamine; D006632:Histamine; D013890:Thiourea; D009638:Norepinephrine; D017259:Dimaprit