Histamina, receptores de histamina e anti-histamínicos: novos conceitos / Histamine, histamine receptors and antihistamines: new concepts

As drogas com ação anti-histamínica estão entre as medicações mais comumente prescritas na prática dermatológica diária, tanto em adultos como em crianças. Este artigo aborda os novos conceitos da função dos receptores de histamina (receptores H1) e discute os efeitos anti-inflamatórios dessas drogas. A segunda geração de anti-histamínicos difere da primeira geração devido a sua elevada especificidade e afinidade pelos receptores H1 periféricos e devido a seu menor efeito no sistema nervoso central, tendo como resultado menores efeitos sedativos. Embora a eficácia dos diferentes anti-histamínicos H1 (anti-H1) no tratamento de doentes alérgicos seja similar, mesmo quando se comparam anti-H1 de primeira e de segunda geração, eles são muito diferentes em termos de estrutura química, farmacologia e propriedades tóxicas. Consequentemente o conhecimento de suas características farmacocinéticas e farmacodinâmicas é importante para a melhor prática médica, especialmente em gestantes, crianças, idosos e doentes com comorbidades.

Drugs with antihistamine action are the most commonly prescribed medication in daily dermatologic practice, both to adults and children. This article addresses new concepts of the role of histamine receptors (H1 receptors) and discusses the anti-inflammatory effects of these drugs. Second generation antihistamines differs from first generation because of their high specificity and affinity for peripheral H1-receptors. Second generation antihistamines are also less likely to produce sedation because they have less effect on the central nervous system. Although the efficacy of the various H1-antihistamines in the treatment of allergic patients is similar, even when comparing first- and second-generation drugs, these drugs are still very different in terms of their chemical structure, pharmacology and toxic properties. Consequently, knowledge of their pharmacokinetic and pharmacodynamic characteristics is essential for a better medical care, especially that offered to pregnant women, children, the elderly, and patients with comorbidities.

role of central endogenous histamine and H[1], H[2] and H[3] receptors on food intake in broiler chickens

The role of endogenous histamine and H[1], H[2] and H[3] central receptors on food intake in broiler chickens was investigated. For this purpose, a probe was used to manipulate the concentration of endogenous histamine by intracerebroventricular [ICV] injection of thioperamide, an H[3] receptor antagonist, and R-alpha-methylhistamine, an H[3] receptor agonist and subsequently the effects of brain histaminergic system on food intake was assessed. Moreover, to determine the receptors involved in histamine-induced feeding behaviour changes, H[1], and H2 blockers were administered to thioperamide-treated chickens. Injection of thioperamide [600 and 300 nmol] decreased food intake dose-dependently [P<0.05]. On the contrary, ICV injection of R-alphamethylhistamine [400 and 200 nmol] increased food intake [P<0.05]. Chlorpheniramine [128 and 256 nmol], a H[1] receptor antagonist, increased food intake [P<0.05]. Famotidine, a H[2] receptor antagonist at 74 or 148 nmol had no effect on food intake but at 296 nmol significantly decreased food intake [P<0.05]. Pretreatment with chlorpheniramine [256 nmol] significantly attenuated thioperamide effects [600 nmol] on food intake [P<0.05]. In conclusion, the results of the present study demonstrated that histamine exerts anorexigenic effects through H[1], but not H[2] receptors in broiler chickens. Furthermore, it was shown that thioperamide through stimulation of synthesis and release of endogenous neuronal histamine can decrease food intake in broiler chickens

Different roles of histamine receptor subtypes in ampullar & isthmic segments of human fallopian tube.

We have studied the influence of both menstrual cycle phase and subtype-selective histamine antagonists on the contractions produced by histamine isolated in human fallopian tubes. Histamine produced tonic contractions of the isolated preparations of both the ampullar and isthmic segments of the human fallopian tube were analyzed. The effects of both histamine and its antagonists were not dependent on the phase of the menstrual cycle. The isolated preparations of the ampullar segment from post menopausal patients were not responsive on histamine. When responding, the ampullar segments were slightly more sensitive to histamine than the isthmic segments. All three subtype selective histamine antagonists (pyrilamine, cimetidine and thioperamide) produced strong inhibition of histamine evoked contractions of the ampullar segment. On the other hand, only pyrilamine strongly inhibited histamine evoked contractions of the isthmic segment. The results of our study suggest that only H1 receptors were responsible for the histamine contractile effect on the isthmic segment and that all three subtypes of histamine receptors were involved in the effect of histamine on the ampullar segment of human fallopian tube.

Hippocampal histamine receptors and conflictive exploration in the rat: studies using the elevated asymmetric plus-maze

The possible role of histamine receptors in the hippocampal formation on the exploratory motivation and emotionality of the rat was studied. An elevated asymmetric plus-maze composed of 4 different arms (no walls, single high wall, high and low walls and two high walls) arranged at 90 degrees angles was used. The exploration score, considered to be an index of exploratory motivation, and the permanency score, considered to be an index of emotionality (anxiety), were determined. Histamine was administered locally into the ventral hippocampus at three different doses (9,45 and 90 nmol). Another group of rats was also microinjected with 45 nmol of pyrilamine (a histamine H1 receptor antagonist) or ranitidine (a histamine H2 receptor antagonist) in addition to 9 nmol of histamine in order to identify the possible type of histamine receptor involved. Histamine administration significantly inhibited the exploration score and increased the permanency score at the doses of 9 and 45 nmol in two of four arms. These effects were completely blocked by the administration of eitheer histamine receptor antagonist. The present results suggest that in the hippocampal formation histamine inhibits exploratory motivation and decreases emotionality by activating both types of histamine receptors. Also, the elvated asymmetric plus-maze appears to be a suitable technique to quantify exploration and possibly "anxiety".

Experimental autoimmune myocarditis: a suitable model to study neuroimmune crosstalk

This review regards the main functional characteristics of hearts subjected to an autoimmune response focusinf especially on the role of T lymphocytes and autoantibodies in the development of cardiac dysfunction. Evidence of a strong association in the onset and time-course of immune response and cardiac dysfunction is presented and the results are viewed comparatively with myocarditis models induced by heart, parasite or virus inoculation. Cardiac damage is evaluated regarding various aspects, namely histologic, immunologic, biochemical, pharmacologic, physiologic. Finally, the model, for its characteristics of resulting from an autoimmune response against the heart with functional consequences, has proved its usefulness to study neuroimmune interaction, mainly the immune to nervous direction, as autoantibodies and T cell-derived factors have a role in cardiac failure.

Involvement of histamine receptors in mediation of histamine induced thermoregulatory response in rats.

At there ambient air temperature range, the rectal temperature changes following infusion of histamine either into lateral ventricle (L.V.) or IVth ventricle (IVth V) were studied. At an ambient temperature range of 19-22 degrees C, hypothermia occurred following histamine infusion either into L.V. or IVth V. Hypothermia elicited from infusion of histamine into L.V. was prevented with pretreatment of H1-receptor blocker (mepyramine), but in case of IVth V, it was prevented with H2-receptor blocker(cimetidine). These H1 and H2-receptor antagonists were ineffective in preventing hypothermia following histamine infusion into either L.V. or IVth V, when the ambient air temperature was maintained low (11-13 degrees C).