Combined use of tertiary amine parasympathomimetics with a quaternary amine parasympatholitic--a new perspective to use parasympathomimetic drugs for systemic analgesia

Pharmazie. 2002 Jul;57(7):485-6.

Abstract

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.

MeSH terms

  • Amines / chemistry
  • Amines / pharmacology*
  • Analgesics / pharmacology*
  • Animals
  • Arecoline / pharmacology
  • Cholinesterase Inhibitors / pharmacology
  • Drug Synergism
  • Female
  • Male
  • Mice
  • Muscarinic Antagonists / pharmacology
  • Pain Measurement / drug effects
  • Parasympatholytics / chemistry
  • Parasympatholytics / pharmacology*
  • Parasympathomimetics / chemistry
  • Parasympathomimetics / pharmacology*
  • Physostigmine / pharmacology
  • Reaction Time / drug effects
  • Scopolamine / pharmacology

Substances

  • Amines
  • Analgesics
  • Cholinesterase Inhibitors
  • Muscarinic Antagonists
  • Parasympatholytics
  • Parasympathomimetics
  • Arecoline
  • Physostigmine
  • Scopolamine