Histamina, receptores de histamina e anti-histamínicos: novos conceitos

Abstract

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. Keywords: Histamine; Histamine H1 receptors antagonists; Histamine receptors; Histamine release; Histamine H1 antagonists, non-sedating; Receptors, histamine H1Resumo: 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. Palavras-chave: Antagonistas da histamina H1 não sedativos; Antagonistas dos receptores H1 de histamina; Histamina; Liberação de histamina; Receptores de histamina; Receptores de histamina H1

Clinically Approved Ion Channel Inhibitors Close Gates for Hepatitis C Virus and Open Doors for Drug Repurposing in Infectious Viral Diseases

“…On the one hand, many diphenyl-piperazines (e.g., chlorcyclizine, cyclizine, and hydroxyzine), cycloheptene-piperidines (e.g., cyproheptadine, ketotifen, loratadine, and desloratadine), and phenothiazines (e.g., mequitazine and trimeprazine) that were recently shown to inhibit HCV cell entry (4, 6) are known to act as H 1 antihistamines (24). Thus, in clinics, these compounds are (or have been) used because of their ability to competitively inhibit the interaction between histamine and the H 1 histamine receptor.…”

“…The histamine receptor is a typical G protein-coupled receptor (GPCR) that, upon binding to histamine, is activated and stimulates several signaling processes. These include the production of inositol 1,4,5-triphosphate (InsP 3 ) and diacylglycerol (DAG), causing an accumulation of intracellular calcium (24,25). Moreover, NF-B-, phospholipase D-, and phospholipase A-dependent pathways can be stimulated by H 1 histamine receptor activation, and they are involved in the development of allergies (24,25).…”

“…These include the production of inositol 1,4,5-triphosphate (InsP 3 ) and diacylglycerol (DAG), causing an accumulation of intracellular calcium (24,25). Moreover, NF-B-, phospholipase D-, and phospholipase A-dependent pathways can be stimulated by H 1 histamine receptor activation, and they are involved in the development of allergies (24,25). H 1 antihistamines are grouped as first-and second-generation drugs, with the latter causing many fewer side effects (24).…”

“…Unlike second-generation H 1 antihistamines, drugs of the first generation cross the blood-brain barrier. They influence the function of muscarinic, ␣-adrenergic, and serotonergic receptors and can modulate cardiac channels, resulting in a relatively broad spectrum of side effects, including sedation, hyperactivity, insomnia, and convulsions (24). Among antihistamines with anti-HCV activity are both first-generation (chlorcyclizine, cyclizine, hydroxyzine, cyproheptadine, ketotifen, mequitazine, and trimeprazine) and second-generation (loratadine and desloratadine) antihistamines (4,6,24), which indicates that both drug classes include molecules that can target HCV.…”

Development and Validation of Ultraviolet Spectrophotometric Method for Determination of Mebhydroline Napadisylate in Tablet Preparations

“…Antihistamines comprise a broad class of pharmacological agents that include the first generation, relatively sedating H 1 antagonists and second generation, less sedating or nonsedating H 1 antagonists [1]. In the manufacture of pharmaceuticals, examination of the active substance level is a requirement that must be met to ensure the quality of drug preparations.…”