Is epibatidine really analgesic? Dissociation of the activity, temperature, and analgesic effects of (+/-)-epibatidine.
The experiments in the present study were designed to determine if the activity, temperature, and analgesic effects of (+/-)-epibatidine treatment could be dissociated. Initially (i.e., 15 min) (+/-)-epibatidine treatment (0.1 mumol/kg = 28 micrograms/kg, IP) impaired rotorod performance, decreased activity, decreased temperature, and increased jump latency (e.g., analgesic effect). For the remaining time points measured (i.e., 30, 60, and 120 min), activity and temperature remained significantly reduced. In contrast, by 120 min (+/-)-epibatidine's effects on rotorod performance and analgesia (jump latency) were not observed. When administered after (+/-)-epibatidine (0.05 mumol/kg, IP), mecamylamine treatment (5 mumol/kg = 1 mg/kg, IP) produced a potentiation of analgesia. This potentiation effect was not observed on activity and temperature measures. The effect of (+/-)-epibatidine treatment (0.1 mumol/kg, IP) was also determined in mice with central nicotinic receptor blockade induced by treatment with chlorisondamine (23 mumol/kg = 10 mg/kg, IP). An (+/-)-epibatidine-induced reduction in activity was not attenuated in chlorisondamine-treated mice and only a minimal effect was observed on (+/-)-epibatidine-induced hypothermia in chlorisondamine-treated mice. In contrast, in chlorisondamine-treated mice (+/-)-epibatidine's analgesic effect was attenuated. Taken together, these data suggest that various centrally mediated effects of (+/-)-epibatidine can be dissociated.
Bannon
A W
AW
Pharmaceutical Products Division, Abbott Laboratories, IL 60064-3500, USA.
Gunther
K L
KL
Decker
M W
MW
D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D001831:Body Temperature / Q000187:drug effects*; D001643:Bridged Bicyclo Compounds / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002714:Chlorisondamine / Q000494:pharmacology; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D010147:Pain Measurement / Q000187:drug effects; D004856:Postural Balance / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects; D011725:Pyridines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013237:Stereoisomerism; D013997:Time Factors
D018712:Analgesics, Non-Narcotic; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D011725:Pyridines; D008464:Mecamylamine; D002714:Chlorisondamine; C082748:epibatidine