Effect of Extra- and Intracellular Calcium Blockers on Histamine and Antigen-Induced Bronchospasms in Guinea Pigs and Rats

Abstract

The extracellular calcium antagonists, nifedipine and verapamil, the mixed extra/intracellular calcium antagonist diazoxide and the intracellular calcium antagonist TMB-8 were studied for their effects on histamine-induced bronchospasm in guinea pigs and on antigen-induced bronchospasms in guinea pigs and rats when administered directly to the tracheobronchial tree. Nifedipine and verapamil inhibited histamine and antigen-induced bronchoconstriction in guinea pigs, and verapamil was effective in preventing antigen-induced bronchospasms in rats. However, using doses of the extracellular blockers which produce these pulmonary effects, significant reduction of blood pressure occurred in both guinea pigs and rats. Diazoxide was inactive against histamine and antigen-induced bronchoconstrictions in guinea pigs. TMB-8 was inactive against histamine and antigen-induced bronchospasm in guinea pigs and rats. These studies demonstrate the antibronchoconstrictor activity of extracellular Ca²⁺ antagonists in guinea pigs and rats, but indicate that intracellular Ca²⁺ antagonists are not antibronchospastic agents in these species in vivo.

Verapamil Induces Calcium Influx in the Trachea

“…It is also shown that extracellular-site Ca 2+ -entry blockers inhibited histamine-and allergen-induced bronchoconstriction, whereas the intracellular-site Ca 2+ -entry blockers did not (24). It was proven that verapamil significantly worsened the bronchoconstriction induced by methacholine in vivo (23). Inhaled verapamil has been reported to produce bronchoconstriction (10,24,25).…”

“…Inversely, other studies showed that VOC-blocking drugs, such as nifedipine, have proved disappointing as a therapy for asthma (19) and have a limited effect in alleviating bronchial constriction (20 -22). It was proven that blockade of L-type Ca 2+ channels at the extracellular (dihydropyridine and benzothiazepine group) rather than intracellular (phenylalkylamine group; e.g., verapamil) surface of the smooth muscle cell membrane may attenuate bronchoconstriction (23). It is also shown that extracellular-site Ca 2+ -entry blockers inhibited histamine-and allergen-induced bronchoconstriction, whereas the intracellular-site Ca 2+ -entry blockers did not (24).…”

Rapid synthesis and biological evaluation of 1,4-dihydropyridine derivatives containing a benzothiazolyl moiety

“…So 1,4-DHPs classes of compounds are excellent starting synthons for the development of antitubercular agents [4][5][6]. As a result, newly synthesized generations of 1,4-DHPs possess different pharmacological activities such as anticancer [7], antidiabetic [8], antianginal [9], bronchodilating [10], neurotropic [11], antiallergic [12], anti-inflammatory [13], acaricidal, insecticidal, bactericidal, herbicidal [14] and other pharmacological activities [15]. These are used extensively in the treatment of angina pectoris, hypertension and arrhythmia [16] and some cardiovascular disorder.…”

Antimony(V) chloride-promoted room temperature aromatization of 1,4-dihydropyridines in non-acidic solvent

“…1 The 1,4-DHPs cause vasorelaxation by blocking voltage-operated calcium channel in smooth muscle cells and also by increasing NO release from the intact endothelium. 2 Recently, some other pharmacological activities have been reported such as: antitumor, 3 bronchodilating, 4 antidiabetic, 5 antiviral 6 and antianginal. 7 The 1,4-DHPs have also been extensively utilised as analogs of NAD(P)H coenzymes to study the mechanism and synthetic potential of various redox processes.…”