Possible Interaction: Adenosine and Morphine

“This may indicate an additive effect on pain reduction when adenosine is given in combination with morphine or ketamine.”

“Further evidence that cAMP accelerated dependence development on morphine was evidenced by the fact that cAMP increased the loss in body weight that occurred after abrupt morphine withdrawal.”

“The administration of cyclic 3', 5'-adenosine monophosphate (cAMP) antagonized the analgetic response of morphine in both nontolerant and tolerant mice and also accelerated the development of tolerance to and physical dependence on morphine induced by morphine pellet implantation.”

“Tolerance enhancement by cAMP was evidenced by the increased amount of morphine to produce analgesia and acceleration in dependence by the decrease in the amount of naloxone to induce precipitated withdrawal jumping after cAMP pretreatment.”

“Furthermore, morphine delayed the inhibition of platelet plug formation under high shear rates (P2Y-Innovance; n = 21; p < 0.004) and abolished the 3-fold prolongation in collagen adenosine diphosphate-induced closure times seen in extensive and rapid metabolizers (n = 16; p = 0.001).”

“… morphine doses (10-40 mg/kg) administered over a 4-… selectively induced a twofold decrease (p<0.00005) in adenosine abundance in the brainstem of C57BL/6 mice, which exhibited symptoms of narcotic drug dependence; … not decrease adenosine abundance in 129Sv1 mice, which do not exhibit symptoms of dependence.”

“On the other hand, a tight interaction has been reported between morphine and adenosine in various paradigms.”

“These results indicate that treatment of morphine in vitro dynamically changes the concentrations of ATP and adenosine in extracellular milieu of astrocytic cells.”

“The P1 purinoceptor agonist, adenosine , was able dose-dependently to reduce morphine withdrawal whereas alpha,beta-methylene ATP (APCPP), a P2 purinoceptor agonist, increased morphine withdrawal.”

“Also, it seems that adenosine acts as a modulator in rCBF regulation of morphine-dependent and morphine withdrawal rats.”

“Conclusion Morphine normally stimulates spinal release of adenosine , a potent antihypersensitivity compound.”

“The authors hypothesized that morphine induces less adenosine release in neuropathic compared with normal rats, explaining its reduced potency and efficacy.”

“The P1 purinoceptor agonist, adenosine , was able dose-dependently to reduce morphine withdrawal whereas alpha,beta-methylene ATP (APCPP), a P2 purinoceptor agonist, increased morphine withdrawal.”