An analysis of the respiratory stimulant effect of physostigmine and neostigmine in the conscious rabbit.

1. The effects of physostigmine and neostigmine, given by continuous intravenous infusion, were studied on respiration in conscious rabbits. 2. Physostigmine (5 mg/kg per min) significantly increased respiration rate, decreased arterial PaCO2 from 25.4 +/- 0.9 to 19.8 +/- 1.5 mmHg, increased PaO2 from 100.3 +/- 1.9 to 108 +/- 3.0 and pH from 7.42 +/- 0.01 to 7.46 +/- 0.01 within 30 min of its infusion. 3. Neostigmine (2.5 mg/kg per min) also decreased PaCO2 and increased PaO2 significantly, but caused a concomitant lactic acidosis, which was associated with the increased muscular activity and fasciculations. 4. The respiratory stimulant effect of neostigmine, but not that of physostigmine, was abolished by hexamethonium 2 X (1.5 mg/kg). Atropine methyl nitrate (1 mg/kg) failed to influence the respiratory stimulant effect of physostigmine, but hyoscine (10 mg/kg) blocked it completely. 5. It is suggested that augmentation of respiratory activity by neostigmine is mediated via peripheral nicotinic receptors in the carotid and aortic bodies. This may occur either through the accumulation of acetylcholine or H+ ions from raised blood lactic acid. 6. It is further suggested that physostigmine stimulates respiration by raising the concentration of acetylcholine in the central nervous system which, in turn, activates muscarinic receptors.