Peripheric receptor agonists after intramuscular administration potentiate analgesic effects of fentanyl and dipyrone as result of stimulation of vagal afferents in gastric mucosa

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Abstract

lntramuscular (i.m.) administration of the central analgesics fentanyl and dipyrone, and also agonists of peripheral receptors: cholecystokinin (ССК), glutamate, АТФ, adrenaline and adenosine, weakly penetrating into CNS, in the minimal effective dose (MED) causes the maximal analgesic effect in the tail-flick test in rats. lntragastric administration of lidocaine, and also the subdiaphragmatic gastric vagotomy increase MED of the agonists of peripheral receptors in 6-1 5 times, but do not change MED of the central analgesics. lt is concluded that the agonists of peripheral receptors after systemic administration cause the central vagal analgesia in which the trigger mechanism is the stimulation of chemoceptors of vagal afferents in gastric mucosa. MED of dipyrone and fentanyl аге decreased in 50-220 times after the combined i.m. administration of each analgesics with ССК, glutamate, АТР, adrenaline and adenosine in threshold, independently noneffective doses, which does not yet affect peripheric nociceptors. lntragastric administration of lidocaine, and also subdiaphragmatic gastric vagotomy completely eliminate analgesic effects of the above mentioned comblnations. lt follows that agonists of peripheral receptors after systemic administration in threshold doses potentiate the central analgesic action of dipyrone and fentanyl as а result of stimulation of chemoceptors of vagal afferents in gastric mucosa.

About the authors

S. Е. Serdyuk

lnstitute of Experimental Medicine of the Russian Academy of Medical Sciences

Author for correspondence.
Email: medaj@eco-vector.com
Russian Federation, St. Petersburg

V. Е. Gmiro

lnstitute of Experimental Medicine of the Russian Academy of Medical Sciences

Email: medaj@eco-vector.com
Russian Federation, St. Petersburg

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