Contribution of beta-lactamase production to the resistance of mycobacteria to beta-lactam antibiotics

Changes in motor function were assessed in male rats after injecting graded doses (100, 200, 400, and 800 mg/kg, IP) of ammonium chloride and ammonium acetate. The effects were correlated with the concentrations of ammonia and glucose in the brain and blood. Spontaneous motor activity and motor coordination were inhibited after injecting 100 and 200 mg/kg, whereas with 400 and 800 mg/kg the animals exhibited convulsive movements. A dose-dependent increase was found in the concentrations of ammonia and glucose in both blood and brain. These were restored, 25 min after treatment, to control levels in the blood and not in the brain. A correlation was found between the time courses of inhibitory motor events and a rise in brain ammonia levels. Convulsant action of ammonium salts was accompanied by a marked elevation of ammonia and glucose concentration in the brain. The findings suggest that detoxication of diffused ammonia is a rate-limiting process in the brain and that ammonia, at toxic concentrations, decreases glucose utilization in the brain, resulting in an inhibition of motor function. A very high concentration of ammonia in the brain, although inhibiting glucose utilization, produces clonic convulsions probably by activating directly the motor neurons.