Study of in vitro and in vitro effects of isradipine in skeletal muscles and interaction with some drugs
Singh, Y.N.; Johnson, A.; Lulf, L.A.; Singh, B.N.
Methods and Findings in Experimental and Clinical Pharmacology 18(8): 499-506
1996
ISSN/ISBN: 0379-0355 PMID: 9044237 Document Number: 465500
The effects of the calcium channel blocker isradipine were studied in the indirectly and directly stimulated mouse diaphragm and in the anesthetized rat to determine its potency, reversibility and interaction with a number of drugs. Initially, it potentiated both indirect and direct twitches followed by a reduction. With tetanic contractions, no potentiation was obtained, only a reduction, which was complete or near complete at the highest concentration tested (10-4 M). In combination, isradipine reduced the IC-50 and IC-90 values for the antibiotics gentamicin, polymyxin B and clindamycin, d-tubocurarine and magnesium ions. Depression of contraction caused by isradipine or in combination could be reversed to varying degrees by washout, elevated calcium ions, neostigmine or 4-aminopyridine. Spontaneous recovery from the effects of isradipine alone or in combination was slow and usually incomplete. For in vivo experiments, severe cardiovascular depressant effects of isradipine limited its exposure to lower concentrations and for shorter periods. Under these conditions, it had no effect on heart rate. However both systolic and diastolic blood pressure were significantly reduced, while pulse pressure was increased After an initial potentiation, muscle contraction was maximally reduced to 55% of control. This study indicates that acute administration of isradipine may aggravate neuromuscular effects of antibiotics, muscle relaxants or hypermagnesemia, although it is unlikely that spontaneous recovery or reversibility of muscular activity by suitable reversal agents will be affected However, prolonged use of the drug may be more difficult to reverse.