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Study of in vitro and in vitro effects of isradipine in skeletal muscles and interaction with some drugs.
Methods Find Exp Clin Pharmacol. 1996 Oct; 18(8):499-506.MF

Abstract

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 IC50 and IC90 values for the antibiotics gentamicin, polymyxin B and clindamycin, d-rubocurarine 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.

Authors+Show Affiliations

College of Pharmacy, South Dakota State University, Brookings, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9044237

Citation

Singh, Y N., et al. "Study of in Vitro and in Vitro Effects of Isradipine in Skeletal Muscles and Interaction With some Drugs." Methods and Findings in Experimental and Clinical Pharmacology, vol. 18, no. 8, 1996, pp. 499-506.
Singh YN, Johnson A, Lulf LA, et al. Study of in vitro and in vitro effects of isradipine in skeletal muscles and interaction with some drugs. Methods Find Exp Clin Pharmacol. 1996;18(8):499-506.
Singh, Y. N., Johnson, A., Lulf, L. A., & Singh, B. N. (1996). Study of in vitro and in vitro effects of isradipine in skeletal muscles and interaction with some drugs. Methods and Findings in Experimental and Clinical Pharmacology, 18(8), 499-506.
Singh YN, et al. Study of in Vitro and in Vitro Effects of Isradipine in Skeletal Muscles and Interaction With some Drugs. Methods Find Exp Clin Pharmacol. 1996;18(8):499-506. PubMed PMID: 9044237.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Study of in vitro and in vitro effects of isradipine in skeletal muscles and interaction with some drugs. AU - Singh,Y N, AU - Johnson,A, AU - Lulf,L A, AU - Singh,B N, PY - 1996/10/1/pubmed PY - 1996/10/1/medline PY - 1996/10/1/entrez SP - 499 EP - 506 JF - Methods and findings in experimental and clinical pharmacology JO - Methods Find Exp Clin Pharmacol VL - 18 IS - 8 N2 - 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 IC50 and IC90 values for the antibiotics gentamicin, polymyxin B and clindamycin, d-rubocurarine 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. SN - 0379-0355 UR - https://www.unboundmedicine.com/medline/citation/9044237/Study_of_in_vitro_and_in_vitro_effects_of_isradipine_in_skeletal_muscles_and_interaction_with_some_drugs_ DB - PRIME DP - Unbound Medicine ER -