flunarizine and lanthanum-chloride

1. 4-Aminopyridine and 3,4-diaminopyridine produced concentration-dependent contraction on guinea-pig isolated ileum incubated in Tyrode solution. The EC30 values were 1.14 x 10(-4) and 1.39 x 10(-4) M, respectively. 2. Calcium channel blockers such as verapamil, diltiazem, nifedipine, flunarizine, and lanthanum chloride antagonized the contracting effect induced by 4-aminopyridine and 3,4-diaminopyridine in guinea-pig isolated ileum. 3. Diazoxide and atropine sulphate behaved similarly as antagonists of the contracting effect induced by 4-aminopyridine and 3,4-diaminopyridine in guinea-pig isolated ileum. 4. It is concluded that the aminopyridines exert their effects through the release of acetylcholine from parasympathetic nerve terminals.

Topics: 4-Aminopyridine; Acetylcholine; Amifampridine; Animals; Atropine; Calcium Channel Blockers; Diazoxide; Diltiazem; Dose-Response Relationship, Drug; Drug Interactions; Female; Flunarizine; Guinea Pigs; Ileum; In Vitro Techniques; Lanthanum; Male; Muscle Contraction; Muscle, Smooth; Nifedipine; Parasympathetic Nervous System; Parasympatholytics; Potassium Channels; Vasodilator Agents; Verapamil

We tested the effects of the calcium antagonists lanthanum, diltiazem, and flunarizine on the development of atherosclerosis in rabbits fed a 2% cholesterol diet. The drugs were given orally and were well tolerated. In the cholesterol control animals, 52.2% of the thoracic aortic intimal surface was Sudan IV positive. This was reduced by 37% (p less than 0.05) with lanthanum, 37% (p less than 0.05) with diltiazem, and 34% (p less than or equal to 0.06) with flunarizine. In all cholesterol-fed animals, the intramural, but not subepicardial, coronary arteries were severely diseased. The extent and distribution of this disease were not altered by the various drug interventions. Thus, the calcium antagonists lanthanum, diltiazem, and flunarizine suppress atherogenesis of the rabbit aorta but have no effect on the extent or distribution of atherosclerosis in the intramural coronary arteries.

Topics: Animals; Aortic Diseases; Arteriosclerosis; Calcium Channel Blockers; Cholesterol, Dietary; Cinnarizine; Coronary Disease; Diltiazem; Female; Flunarizine; Lanthanum; Organ Size; Rabbits