Toxicity of methylimidazoles

Abstract

Toxic manifestations of ammoniated invert molasses in cattle can be simulated in laboratory animals such as rabbits, mice and day-old chicks by administering 4-methylimidazole (4-me-I). This compound, which results from the interaction of reducing sugars with ammonia, has previously been isolated from ammoniated invert molasses in addition to other compounds such as pyrazine derivatives. The mouse seems to be the most practical animal for testing the neurological signs produced by 4-me-I. The convulsive death produced by 4-me-I in the rabbit is characterized by the typical epileptiform EEG (high voltage, high frequency) concomitant with clonic and tonic seizures followed by tonic extensor seizure (high voltage, low frequency peaks) and terminal respiratory paralysis. This fatal course can be prevented by pentobarbital sodium and chlordiazepoxide. Diphenylhydantoin did not protect mice against 4-me-I seizures and death, in contrast to phenobarbital sodium and chlordiazepoxide. 4-Methylimidazole had approximately one-fourth the convulsant potency of pentylenetetrazole. Imidazole, 1-methylimidazole, and 2-methylimidazole produced neurologic effects in mice similar to those caused by 4-me-I, but they were less potent as convulsants. The spontaneous motor activity of mice treated with 4-me-I was reduced to about 50% during the period preceding the seizures. In rabbits, 4-me-I decreased heart rate as much as 33% below the control and increased the respiratory rate to three times the control value during the period preceding the convulsions.