Pharmacological analysis of alpha(2)-adrenoceptor subtypes mediating analgesic, anti-inflammatory and gastroprotective actions

Inflammopharmacology. 2009 Jun;17(3):171-9. doi: 10.1007/s10787-009-0003-2. Epub 2009 Jun 13.

Abstract

Our previous findings suggest that alpha(2)-adrenoceptor stimulants induce gastroprotective action, the effect is likely to be mediated by alpha(2B)-adrenoceptor subtype. Clonidine (0.094 micromol/kg p.o.) and rilmenidine (0.014 micromol/kg p.o.) in gastroprotective dose range, as well as ST-91 (2.2 micromol/kg p.o.), a clonidine analogue showing higher affinity to alpha(2B)-adrenoceptor subtype than to alpha(2A)-one, inhibited the carrageenan-induced hyperalgesia in Randall-Selitto test, the antinociceptive action was reversed by yohimbine (5 micromol/kg s.c.) and the alpha(2B)-adrenoceptor antagonist prazosin (0.24 micromol/kg i.p.). Similarly, clonidine and rilmenidine in the same dose range reduced the oedema formation induced by carrageenan, yohimbine and the alpha(2A)-adrenoceptor antagonist BRL-44408 (3 micromol/kg i.p.) inhibited the anti-inflammatory effect; however, prazosin failed to affect it. These results suggest that alpha(2B/C)-like adrenoceptor subtype may be involved in the antihyperalgesic action, but not in the antiphlogistic effect of alpha(2)-adrenoceptor stimulants. The later effect may be mediated by alpha(2A)-like adrenoceptor subtype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-2 Receptor Agonists*
  • Adrenergic alpha-2 Receptor Antagonists
  • Adrenergic alpha-Agonists / therapeutic use
  • Analgesics / therapeutic use*
  • Animals
  • Anti-Inflammatory Agents / therapeutic use*
  • Anti-Ulcer Agents / therapeutic use*
  • Clonidine / analogs & derivatives
  • Clonidine / therapeutic use
  • Disease Models, Animal
  • Edema / chemically induced
  • Edema / drug therapy*
  • Gastrointestinal Motility / drug effects
  • Gastrointestinal Motility / physiology
  • Hyperalgesia / chemically induced
  • Hyperalgesia / drug therapy*
  • Male
  • Oxazoles / therapeutic use
  • Rats
  • Rats, Wistar
  • Receptors, Adrenergic, alpha-2 / physiology
  • Rilmenidine
  • Stomach Ulcer / chemically induced
  • Stomach Ulcer / drug therapy*

Substances

  • Adrenergic alpha-2 Receptor Agonists
  • Adrenergic alpha-2 Receptor Antagonists
  • Adrenergic alpha-Agonists
  • Analgesics
  • Anti-Inflammatory Agents
  • Anti-Ulcer Agents
  • Oxazoles
  • Receptors, Adrenergic, alpha-2
  • ST 91
  • Clonidine
  • Rilmenidine