Effect of clonidine on induced cough and bronchoconstriction in guinea pigs and healthy humans.
We examined the effects of the alpha 2-receptor agonist clonidine, administered orally and by inhalation, on citric acid- and capsaicin-induced reflexes in guinea pigs and healthy human subjects. In groups (n = 8-10) of conscious guinea pigs, oral clonidine (10 and 100 micrograms/kg) was without effects, whereas inhaled clonidine (10-1,000 microM) caused a concentration-dependent inhibition of citric acid-induced cough (coughs during 3 min: control, 6.5 +/- 0.9; 1,000 microM clonidine, 1.7 +/- 1.0; P < 0.05) and reflex bronchoconstriction (time to onset of bronchoconstriction: control, 191 +/- 24 s; 1,000 microM clonidine, 317 +/- 33 s; P < 0.05). The inhibitory effect of inhaled clonidine on both reflexes was completely reversed by pretreatment with yohimbine but not with prazosin. In 12 healthy human volunteers, oral clonidine (150 mg) caused a significant fall in supine and erect systolic blood pressure and a significant increase in drowsiness as measured on a visual analogue scale 1 and 2 h after administration. Despite these effects, oral clonidine had no effect on capsaicin-induced cough or reflex bronchoconstriction in humans. In contrast to the effects in guinea pigs, inhaled clonidine (281 microM) had no effect on capsaicin-induced cough or reflex bronchoconstriction in humans. These data suggest that peripheral alpha 2-receptors exert an inhibitory effect on sensory neurotransmission in the guinea pig but not in the healthy human airway, indicating an important difference between the two species.
O'Connell
F
F
Department of Clinical Pharmacology, Royal Postgraduate Medical School, London, United Kingdom.
Thomas
V E
VE
Fuller
R W
RW
Pride
N B
NB
Karlsson
J A
JA
D000280:Administration, Inhalation; D000284:Administration, Oral; D058669:Adrenergic alpha-2 Receptor Antagonists; D000328:Adult; D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D016084:Bronchoconstriction / Q000187:drug effects*; D002211:Capsaicin; D002951:Citrates; D019343:Citric Acid; D003000:Clonidine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D003371:Cough / Q000139:chemically induced / Q000517:prevention & control*; D005260:Female; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D011224:Prazosin / Q000494:pharmacology; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects; D013045:Species Specificity; D015016:Yohimbine / Q000494:pharmacology
D058669:Adrenergic alpha-2 Receptor Antagonists; D002951:Citrates; D018341:Receptors, Adrenergic, alpha-2; D019343:Citric Acid; D015016:Yohimbine; D003000:Clonidine; D002211:Capsaicin; D011224:Prazosin