Paper Information

Title:  DETERMINATION OF THE COMBINED EFFECT OF FELODIPINE AND A1 ADENOSINE RECEPTOR AGONISTS OR A2A ADENOSINE RECEPTOR ANTAGONIST ON MORPHINE WITHDRAWAL SYNDROME
Type: POSTER
Author(s): MOHADES GISOU*,KHALILI P.,MASOUMI MOGHADAM L.A.,AHMADIASL N.,RASI S.
 
 *DRUG APPLIED RESEARCH CENTER, TABRIZ UNIVERSITY OF MEDICAL SCIENCES
 
Name of Seminar: IRANIAN CONGRESS OF PHYSIOLOGY AND PHARMACOLOGY
Type of Seminar:  CONGRESS
Sponsor:  PHYSIOLOGY AND PHARMACOLOGY SOCIETY, MASHHAD UNIVERSITY OF MEDICAL SCIENCE
Date:  2009Volume 19
 
 
Abstract: 

The opiate withdrawal syndrome appears when the administration of opiates is discontinued abruptly or when an opiate antagonist is administered. Adenosine is a neuromodulator in the central nervous system that reduces opioid withdrawal symptoms. Dihydropyridine calcium channel antagonists also have protective effects against the morphine withdrawal syndrome. We evaluated the role of the purinergic system by using A1 receptor agonist (CCPA) and A2A receptor antagonist (SCH58261) alone or in combination with a calcium channel blocker (Felodipine) to assess their effect on morphine withdrawal syndrome. Male mice received increasing doses of morphine sulphate subcutaneously (sc); the withdrawal syndrome was evoked by naloxone (4 mg/kg ip). Animals were observed for 30 min for jumping behavior and diarrhea. CCPA (0.5 mg/kg ip), SCH 58261 (1 mg/kg ip) were given 10 min and felodipine (2.5, 5, 10 mg/kg ip) 30 min before naloxone. In combination therapy, mice were treated with felodipine 5 mg/kg and CCPA or SCH58261 before naloxone. In the locomotor studies, SCH 58261 and CCPA significantly reduced jumping. CCPA also reduced diarrhea significantly but SCH 58261 had no effect. Felodipine decreased jumping and diarrhea significantly. The effects of 2.5 and 5 mg/kg doses of felodipine, on reducing these symptoms were significant. Combination therapy with felodipine and CCPA or SCH58261 has also significant effects on jumping and diarrhea. Our results emphasize that A1 and A2A adenosine receptors mediate the effects of adenosine on opiate withdrawal syndrome. Ca2+ channel blockers suppress the behavioural expressions of morphine withdrawal. Felodipine in combination with SCH58261 and CCPA decreased morphine withdrawal symptoms. But the potentiating effect was observed just in felodipine and SCH combination therapy.

 
Keyword(s): MORPHINE WITHDRAWAL SYNDROME, CALCIUM CHANNEL BLOCKER, ADENOSINE
 
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