Combined use of tertiary amine parasympathomimetics with a quaternary amine parasympatholitic--a new perspective to use parasympathomimetic drugs for systemic analgesia.
The interactions on antinociception between a muscarinic agonist arecoline (arec), an anticholinesterase physostigmine (physo) which both cross CNS, and a peripherally acting antimuscarinic hyoscine-N-butyl bromide (hyo), were assessed by tail flick test in mice. All drugs were administered intraperitoneally (i.p.). While hyoscine-N-butyl bromide (0.15 and 4.00 mg/kg, i.p.) did not produce antinociception, physostigmine salicylate (0.3 mg/kg, i.p.) and arecoline hydrobromide (8.00 mg/kg, i.p.) exerted significant antinociceptive effect. In combined applications, physo + hyo (0.075 + 0.15; 0.15 + 0.30; 0.30 + 0.60 mg/kg) and arec + hyo (1.00 + 0.50; 2.00 + 1.00; 4.00 + 2.00; 8.00 + 4.00 mg/kg), respectively, produced significant antinociception and the tail flick latencies produced by physo 0.30 + hyo 0.60 mg/kg and arec 8.00 + hyo 4.00 mg/kg were not significantly different from those of physo 0.30 mg/kg and arec 8.00 mg/kg, respectively, showing that hyo did not antagonise the antinociceptive effects of physo and arec. We believe that combining an centrally acting cholinergic drug applied systemically with a peripherally acting (quaternary amine) antimuscarinic compound might be used as an effective analgesic in clinical practice.
Tekol
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Department of Pharmacology, Faculty of Medicine, Erciyes University, Kayseri, Turkey. ytekol@erciyes.edu.tr
Eminel
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S
D000588:Amines / Q000737:chemistry / Q000494:pharmacology*; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001115:Arecoline / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D004357:Drug Synergism; D005260:Female; D008297:Male; D051379:Mice; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects; D010276:Parasympatholytics / Q000737:chemistry / Q000494:pharmacology*; D010277:Parasympathomimetics / Q000737:chemistry / Q000494:pharmacology*; D010830:Physostigmine / Q000494:pharmacology; D011930:Reaction Time / Q000187:drug effects; D012601:Scopolamine / Q000494:pharmacology
D000588:Amines; D000700:Analgesics; D002800:Cholinesterase Inhibitors; D018727:Muscarinic Antagonists; D010276:Parasympatholytics; D010277:Parasympathomimetics; D001115:Arecoline; D010830:Physostigmine; D012601:Scopolamine