Developmental toxicity of nondepolarizing muscle relaxants in cultured rat embryos

Evidence of developmental toxicity of clinically used nondepolarizing muscle relaxants was sought in rat embryos grown in culture. Embryos were explanted at 8 AM on day 9 of gestation (presomite stage, plug day = day 0), and were cultured in rotating bottles with medium containing various concentrat...

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Bibliographic Details
Published in:Anesthesiology (Philadelphia) 1992-06, Vol.76 (6), p.999-1003
Main Authors: FUJINAGA, M, BADEN, J. M, MAZZE, R. I
Format: Article
Language:English
Subjects:
Animals
Atracurium - toxicity
Biological and medical sciences
Drug toxicity and drugs side effects treatment
Embryo, Mammalian - drug effects
Embryonic and Fetal Development
Female
In Vitro Techniques
Male
Medical sciences
Miscellaneous (drug allergy, mutagens, teratogens...)
Neuromuscular Nondepolarizing Agents - toxicity
Pancuronium - toxicity
Pharmacology. Drug treatments
Rats
Rats, Inbred Strains
Tubocurarine - toxicity
Vecuronium Bromide - toxicity
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Summary:Evidence of developmental toxicity of clinically used nondepolarizing muscle relaxants was sought in rat embryos grown in culture. Embryos were explanted at 8 AM on day 9 of gestation (presomite stage, plug day = day 0), and were cultured in rotating bottles with medium containing various concentrations of d-tubocurarine, pancuronium, atracurium, and vecuronium. At 10 AM on day 11 of gestation (forelimb bud stage), culture was terminated and embryos were examined for general morphology. Treatment with tested agents resulted in dose-dependent developmental toxicity; namely, growth retardation seen as decreased crown-rump length, decreased number of somite pairs, and morphologic abnormalities. However, the concentrations that caused toxicity were at least 30-fold greater than serum concentrations clinically achieved in the mother. We conclude that these muscle relaxants have a low potential for causing developmental toxicity during organogenesis.
ISSN:0003-3022
1528-1175
DOI:10.1097/00000542-199206000-00021