Paper Information

Title: 

STUDY OF DICLOFENAC EFFECTS ON NEUROMUSCULAR TRANSMISSION BY IN VIVO AND IN VITRO METHODS

Type: SPEECH
Author(s): VATANPOUR H.*,JALALI A.,HOUSHDAR TEHRANI M.H.,HOUSHI S.,MAHDAVI F.,MOUSAVI Z.,TANBAKOUSAZAN F.
 
 *DEPT. OF PHARMACOLOGY AND TOXICOLOGY, FACULTY OF PHARMACY, SHAHEED BEHESHTI UNIV. OF MED. SCI., TEHRAN
 
Name of Seminar: IRANIAN CONGRESS OF PHYSIOLOGY AND PHARMACOLOGY
Type of Seminar:  CONGRESS
Sponsor:  PHYSIOLOGY AND PHARMACOLOGY SOCIETY, MASHHAD UNIVERSITY OF MEDICAL SCIENCE
Date:  2007Volume 18
 
 
Abstract: 

Introduction: Within the non steroidal anti-inflammatory drugs, the diclofenac sodium ampoule has already been used as an anti-pyretic and analgesic drug in Iran. A number of reports from clinical using of this ampoule were received by ministry of health showed that this drug produces profound adverse effects ranging from myonecrotic, severe pain and fascia infection to sustained inability of muscle-nerve at the site of injection which occasionally led to irreversible localize paralysis. Therefore its utilization was banned for those reasons from 1999. However, its etiology is still unknown and various factors have been proposed to have a role in its development.
Methods: In the current study, the directly effects of diclofenac on the neuromuscular transmission were investigated by the twitch tension technique using the chick biventer cervices (CBC) preparation in vitro (0.02, 0.2, 2 and 20 mg/ml) and the Tibilais muscle of mice in vivo at different concentrations (25, 75, 125, 250 and 750mg/kg).
Results: 0.02-0.2 mg/ml of diclofenac did not produce a significant effect (P>0.05) on nerve-mediated twitch and contracture of the CBC preparation. But in response to indirect stimulation at more concentrations 2-20mg/ml, the twitches were increased concentration dependently first and blocked consequently which led to reversible complete blockage. In order to determination of post or presynaptic effects, the effects of the different dicofenac concentrations on contractile response of the CBC to submaximal concentration of exogenous acetylcholine, carbachol and potassium chloride were obtained and compared to the initial responses without diclofenac addition. The inhibitory effects of higher concentrations of the drug are likely to be due to postsynaptic which affect muscle in the CBC muscle preparation. However, its presynaptic effects cannot be excluded.
Conclusions: Our obtained results from the in vivo study also suggest that diclofenac directly affect neuromuscular transmission in origin as evidenced by the counteraction in motor coordination of the Tibilais muscle of mice. While, diclofenac (with and without excipients) has same manner inhibitory effects, therefore, diclofenac neuromuscular adverse effects, as proposed earlier are attributed to the drug and not associated to other material or pharmaceutical process used for its formulation.

 
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