Microwave facilitation of methylatropine antagonism of central cholinomimetic drug effects.
Pilocarpine-induced hypothermia and oxotremorine-induced tremors in mice are central cholinomimetic drug effects that are readily blocked by the muscarinic antagonist atropine. However, the quaternary ammonium derivative of atropine, methylatropine, is unable to block these cholinomimetic drug effects by virture of its inability to penetrate the blood-brain barrier (BBB) and blood-cerebral spinal fluid barrier (B-CSFB). Dose-response curves for pilocarpine and oxotremorine effects are not appreciably affected either by pretreatment with methylatropine (1.0 mg/kg) or by exposure to moderate-level microwave irradiation (2.45 GHz, 23.7 W/kg, CW, 10-min exposure). However, in mice receiving both the methylatropine pretreatment and microwave irradiation, the dose-response curves for both pilocarpine and oxotremorine effects were significantly shifted to the right, signifying a central anticholinergic action by methylatropine. These data indicate that a single acute exposure to a thermogenic level of microwave irradiation facilitates methylatropine antagonism of centrally mediated cholinomimetic drug effects. One possible explanation for this observation is that microwave radiation may enhance passage of quaternary ammonium compounds like methylatropine across the BBB and B-CSFB.
D000818:Animals; D001286:Atropine Derivatives / Q000494:pharmacology*; D001812:Blood-Brain Barrier / Q000528:radiation effects; D008297:Male; D051379:Mice; D008872:Microwaves; D010095:Oxotremorine / Q000037:antagonists & inhibitors; D010276:Parasympatholytics / Q000494:pharmacology; D010277:Parasympathomimetics / Q000037:antagonists & inhibitors*; D010862:Pilocarpine / Q000037:antagonists & inhibitors
D001286:Atropine Derivatives; D010276:Parasympatholytics; D010277:Parasympathomimetics; D010862:Pilocarpine; D010095:Oxotremorine; C006649:methylatropine