Effects of inhaled alpha 2-adrenoceptor and GABAB receptor agonists on citric acid-induced cough and tidal volume changes in guinea pigs.
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.
Department of Pharmacology, Monash University, Clayton, Australia.
J K
JK
Callaway
R G
RG
King
D000109:Acetylcholine / Q000494:pharmacology; D000280:Administration, Inhalation; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001381:Azepines / Q000008:administration & dosage / Q000494:pharmacology; D001418:Baclofen / Q000008:administration & dosage / Q000494:pharmacology; D002951:Citrates / Q000633:toxicity*; D019343:Citric Acid; D003371:Cough / Q000139:chemically induced / Q000188:drug therapy*; D006168:Guinea Pigs; D008297:Male; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D012119:Respiration / Q000187:drug effects; D013990:Tidal Volume / Q000187:drug effects*; D014991:Xylazine / Q000008:administration & dosage / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D001381:Azepines; D002951:Citrates; D011963:Receptors, GABA-A; D019343:Citric Acid; D014991:Xylazine; D015016:Yohimbine; D005680:gamma-Aminobutyric Acid; C024763:talipexole; D001285:Atropine; D001418:Baclofen; D000109:Acetylcholine