Effects of inhaled alpha 2-adrenoceptor and GABAB receptor agonists on citric acid-induced cough and tidal volume changes in guinea pigs

Eur J Pharmacol. 1992 Sep 22;220(2-3):187-95. doi: 10.1016/0014-2999(92)90747-r.

Abstract

The effects of alpha 2-adrenoceptor and GABA receptor agonists on citric acid-induced cough and increased tidal volume were investigated in conscious guinea pigs. Inhalation of low doses of B-HT 920 (5-allyl-2-amino 5,6,7,8-tetrahydro-4H-thiazolo[4,5-d]azepine dihydrochloride), and xylazine significantly inhibited citric acid-induced cough and tidal volume increases. Intraperitoneal administration of higher doses of B-HT 920 than those given by aerosol were ineffective. The inhibitory effects of B-HT 920 were antagonised by prior intraperitoneal administration of yohimbine, but not atropine. Inhalation of GABA or baclofen inhibited tidal volume increases, but had no effect on cough. Inhaled alpha 2-adrenoceptor or GABA agonists had no effect on the reduced respiratory rate after citric acid inhalation. It is concluded that alpha 2-adrenoceptor agonists inhibit cough via a mechanism which may not be related to their ability to reduce citric acid-induced tidal volume increases, since GABA and baclofen inhibited tidal volume increases but not cough. We suggest that alpha 2-adrenoceptor agonists may have therapeutic potential in the treatment of cough.

MeSH terms

  • Acetylcholine / pharmacology
  • Administration, Inhalation
  • Adrenergic alpha-Agonists / pharmacology*
  • Adrenergic alpha-Agonists / therapeutic use
  • Animals
  • Atropine / pharmacology
  • Azepines / administration & dosage
  • Azepines / pharmacology
  • Baclofen / administration & dosage
  • Baclofen / pharmacology
  • Citrates / toxicity*
  • Citric Acid
  • Cough / chemically induced
  • Cough / drug therapy*
  • Guinea Pigs
  • Male
  • Receptors, GABA-A / drug effects
  • Receptors, GABA-A / metabolism*
  • Respiration / drug effects
  • Tidal Volume / drug effects*
  • Xylazine / administration & dosage
  • Xylazine / pharmacology
  • Yohimbine / pharmacology
  • gamma-Aminobutyric Acid / administration & dosage
  • gamma-Aminobutyric Acid / pharmacology

Substances

  • Adrenergic alpha-Agonists
  • Azepines
  • Citrates
  • Receptors, GABA-A
  • Citric Acid
  • Xylazine
  • Yohimbine
  • gamma-Aminobutyric Acid
  • talipexole
  • Atropine
  • Baclofen
  • Acetylcholine