Atypical antipsychotics such as olanzapine and clozapine are effective at treating the multiple domains of schizophrenia, with a low risk of extra-pyramidal side-effects. However a major downfall to their use is metabolic side-effects particularly weight gain/obesity, which occurs by unknown mechanisms. The present paper explores the potential candidature of histaminergic neurotransmission in t...

Use of molecular pharmacology to reprofile older drugs discovered before the advent of recombinant technologies is a fruitful method to elucidate mechanisms of drug action, expand understanding of structure-activity relationships between drugs and receptors, and in some cases, repurpose approved drugs. The H3 histamine receptor is a G-protein-coupled receptor (GPCR) primarily expressed in the c...

conclusions cyclosom and histamine synergistically exert catalepsy in old rats. in light of these data, the combination of the decreased brain level of somatostatin and increased brain level of histamine may be of pathogenic relevance for extrapyramidal signs in pd. results cyclosom (0.2, 1.0, and 5.0 µg) and histamine (1.0 and 10.0 µg) alone were ineffective in both young and old animals. in c...

Histamine H3 receptors play an important role in biological functions. The aim of this research was to examine whether histamine H3 receptors can be visualized in vivo and in vitro with [18F]3-(1H-imidazol-4-yl)propyl 4-fluorobenzyl ether (fluoroproxyfan). [18F]Fluoroproxyfan was synthesized with high specific activity using [18F]benzyl bromide. The binding of [18F]fluoroproxyfan to rat brain h...

Ciproxifan, i.e., cyclopropyl-(4-(3-1H-imidazol-4-yl)propyloxy) phenyl) ketone, belongs to a novel chemical series of histamine H3-receptor antagonists. In vitro, it behaved as a competitive antagonist at the H3 autoreceptor controlling [3H]histamine release from synaptosomes and displayed similar Ki values (0.5-1.9 nM) at the H3 receptor controlling the electrically-induced contraction of guin...

Data from rat models for alcohol preference and histidine decarboxylase knockout (HDC KO) mice suggest that brain histamine regulates alcohol-related behaviors. Histamine levels are higher in alcoholpreferring than alcohol non-preferring rat brains, and expression of histamine H3 receptor is different in key areas for addictive behavior. Histamine H3 receptor inverse agonists decrease alcohol r...

The preoptic area/anterior hypothalamus, a region that contains neurons that control thermoregulation, is the main locus at which histamine affects body temperature. Here we report that histamine reduced the spontaneous firing rate of GABAergic preoptic neurons by activating H3 subtype histamine receptors. This effect involved a decrease in the level of phosphorylation of the extracellular sign...

Restraint-induced stress (RS) increases histamine concentration in the brain. There is no previous report regarding the role of histamine receptors in immunomodulatory effect of RS. In the present study the role of brain histamine receptors on reduction of humoral and cellular immune function induced by RS was evaluated. For this purpose male Wistar rats (200-250 g) were immunized with sheep re...