Effects of single and long-term theophylline treatment on the threshold of mechanical nociception: contribution of adenosine A1 and alpha2-adrenoceptors.
The effects of single and long-term treatment with theophylline as well as the influence of adenosine A1 receptor agonist cyclopentyladenosine (CPA) and a-adrenergic receptor antagonists prazosin and yohimbine were assessed in the paw pressure test in rats. Both single (37.5 and 75 mg/kg) and long-term (75 mg/kg/day, 14 days i.p.) theophylline treatments exerted antinociceptive effect by increasing the mechanical pain threshold. Single treatment of theophylline (75 mg/kg) antagonized the antinociceptive effect of CPA (0.1 mg/kg); CPA (0.1 mg/kg) abolished the theophylline-induced antinociception. Chronic treatment with theophylline did not change the antinociceptive effect of CPA, while CPA decreased the theophylline antinociception. Yohimbine (0.5 mg/kg), an a 2-adrenoceptor antagonist, diminished the antinociception of a single dose (75 mg/kg) of theophylline, whereas prazocin, an a 1-adrenoceptor antagonist, did not affect it. These results suggest that adenosine A1 and a 2-adrenoceptors take part in the antinociception induced by a single dose of theophylline. The antinociception induced by chronic theophylline treatment probably has a more complex mechanism in which the involvement of adenosine A1.
Pechlivanova
D M
DM
Laboratory Experimental Psychopharmacology, Institute of Physiology, Bulgarian Academy of Sciences, Sofia, Bulgaria. iph@bio.bas.bg
Georgiev
V P
VP
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D058907:Adenosine A1 Receptor Agonists; D058916:Adenosine A1 Receptor Antagonists; D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D008297:Male; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects*; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043682:Receptor, Adenosine A1 / Q000378:metabolism*; D043705:Receptor, Adenosine A2A / Q000378:metabolism*; D013806:Theophylline / Q000008:administration & dosage / Q000494:pharmacology*
D058907:Adenosine A1 Receptor Agonists; D058916:Adenosine A1 Receptor Antagonists; D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D000700:Analgesics; D043682:Receptor, Adenosine A1; D043705:Receptor, Adenosine A2A; C048599:N(6)-cyclopentyladenosine; D013806:Theophylline; D000241:Adenosine; D011224:Prazosin