kelp brands

Molecular formula: C28H31FN4O

Astemizole competes with histamine for binding at H₁-receptor sites in the GI tract, uterus, large blood vessels, and bronchial muscle. This reversible binding of astemizole to H₁-receptors suppresses the formation of edema, flare, and pruritus resulting from histaminic activity. As the drug does not readily cross the blood-brain barrier and preferentially binds at H1 receptors in the peripehery rather than within the brain, CNS depression is minimal. Astemizole may also act on H₃-receptors, producing adverse effects. Antihistamines are effective therapy against histamine-mediated conditions, including seasonal and perennial allergic rhinitis and chronic urticaria. They may also have a therapeutic role to play in asthma. Until recently all antihistamines produced some degree of drowsiness, as well as having anticholinergic side effects. Several non-sedating antihistamines have now been developed. Evidence suggests that their freedom from central nervous system effects is due to their lack of penetration of the blood brain barrier. They also have no appreciable binding to cholinergic receptors. Two of these non-sedating antihistamines, terfenadine and astemizole, have novel binding characteristics with the histamine H1 receptor, exhibiting irreversible binding at higher concentrations. In humans astemizole has a remarkably long half-life of elimination, on the order of 12 to 18 days for metabolites. Clinical trials have demonstrated that these newer antihistamines are as effective as classical antihistamines and that they have no greater incidence of central nervous system or anticholinergic side effects than placebo. QT interval prolongation and torsade de pointes are associated with astemizole intake and have been ascribed to block the repolarizing K+ currents, specifically the rapidly activating component of the delayed rectifier iKr. ... The perforated patch clamp recording technique was used to study the effects of desmethylastemizole (20 nmol/liter) on action potentials and iKr in isolated rabbit ventricular myocytes. Desmethylastemizole produced action potential prolongation and the induction of plateau early afterdepolarizations. Under voltage clamp conditions, desmethylastemizole suppressed iKr amplitude by approximately 65%. The drug E-4031 (100 nmol/liter), which selectively blocks iKr, had a similar effect on current amplitude. Desmethylastemizole, the major astemizole metabolite, blocks the repolarizing K+ current iKr with high affinity. The clinical observation of QT prolongation and torsade de pointes found with astemizole intake may principally be caused by the proarrhythmic effects of its metabolite desmethylastemizole. Astemizole /has/ been recognized in rare cases to induce the syndrome of torsades de pointes, i.e. QT interval prolongation and life-threatening ventricular tachycardia. /It/ was found to prolong cardiac repolarization when its metabolic elimination was impaired, such as by liver disease or drugs that inhibit the 3A family of cytochrome P450. In vitro studies indicate that this action is due to blockade of one or more of the cardiac potassium channels that determine the duration of the action potential.

Source: PubChem (NCBI) · compound 2247