The influence of Bay K 8644 treatment on (+/-)-epibatidine-induced analgesia.
The purpose of this investigation was to determine if analogous to (-)-nicotine's analgesic effect, the analgesic effect of the recently characterized potent nicotinic acetylcholine receptor (nAChR) agonist (+/-)-epibatidine was altered in response to treatment with the calcium channel agonist (+/-)-Bay K 8644. In addition, the effects of the enantiomers, (+)-Bay K 8644, reported to be a calcium channel antagonist, and (-)-Bay K 8644, reported to be a calcium channel agonist were examined. (+/-)-Bay K 8644 (2.8 mumol/kg; i.p.) produced a large analgesic response in mice in the hot-plate paradigm that rapidly dissipated by 30 min after treatment. This analgesic effect of (+/-)-Bay K 8644 was not prevented by pre-treatment with the nicotinic antagonist mecamylamine (5 mumol/kg; i.p.). Treatment with non-analgesic doses of the calcium channel agonists (+/-)- and (-)-Bay K 8644 (1.4 mumol/kg; i.p.) significantly potentiated the analgesic effect of (+/-)-epibatidine (0.05 mumol/kg; i.p.). Potentiation of (+/-)-epibatidine's analgesic effect occurred when the agonists were administered prior to (+/-)-epibatidine or after (+/-)-epibatidine as long as analgesia testing was conducted 15 to 30 min after Bay K 8644 treatment. Pre-treatment with the calcium channel antagonist (+)-Bay K 8644 was found to attenuate (+/-)-epibatidine-induced analgesia. When given after (+/-)-epibatidine, (+)-Bay K 8644 had no effect on (+/-)-epibatidine's analgesic effect. These data provide additional in vivo evidence that altering calcium dynamics can modulate neuronal nAChR function.
Bannon
A W
AW
Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, IL 60064-3500, USA.
Gunther
K L
KL
Decker
M W
MW
Arneric
S P
SP
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000698:Analgesia; D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic; D015220:Calcium Channels / Q000187:drug effects; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D018722:Nicotinic Agonists / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D013997:Time Factors
D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D015220:Calcium Channels; D018722:Nicotinic Agonists; D011725:Pyridines; D008464:Mecamylamine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C082748:epibatidine