BACKGROUND: Administration of drugs blocking muscarinic plus neuronal nicotinic acetylcholine receptors (e.g., atropine and mecamylamine) does not affect the MAC of isoflurane. Although this implies that acetylcholine receptors do not mediate the immobility produced by inhaled anesthetics, another interpretation is possible. Sub-MAC concentrations of isoflurane alone profoundly block acetylcholine receptors, allowing for the possibility that atropine and mecamylamine have no effect because the receptors already are blocked. METHODS: In the present study, we indirectly tested this possibility by measuring the capacity of acetylcholine receptor blockade to decrease the anesthetic requirement for etomidate, an anesthetic thought to act solely by enhancing the effect of gamma-aminobutyric acid on gamma-aminobutyric acid(A) receptors. RESULTS: Administration of 10 mg/kg atropine plus 5 mg/kg mecamylamine did not change the infusion rate of etomidate, or the blood or brain concentrations of etomidate required to produce immobility in rats. CONCLUSION: Acetylcholine receptors do not mediate the capacity of anesthetics to produce immobility in the face of noxious stimulation.
BACKGROUND: Administration of drugs blocking muscarinic plus neuronal nicotinic acetylcholine receptors (e.g., atropine and mecamylamine) does not affect the MAC of isoflurane. Although this implies that acetylcholine receptors do not mediate the immobility produced by inhaled anesthetics, another interpretation is possible. Sub-MAC concentrations of isoflurane alone profoundly block acetylcholine receptors, allowing for the possibility that atropine and mecamylamine have no effect because the receptors already are blocked. METHODS: In the present study, we indirectly tested this possibility by measuring the capacity of acetylcholine receptor blockade to decrease the anesthetic requirement for etomidate, an anesthetic thought to act solely by enhancing the effect of gamma-aminobutyric acid on gamma-aminobutyric acid(A) receptors. RESULTS: Administration of 10 mg/kg atropine plus 5 mg/kg mecamylamine did not change the infusion rate of etomidate, or the blood or brain concentrations of etomidate required to produce immobility in rats. CONCLUSION: Acetylcholine receptors do not mediate the capacity of anesthetics to produce immobility in the face of noxious stimulation.