The Indirect Inhibition of Protein Synthesis in Vivo by Chlorpromazine.

The inhibition of protein synthesis in the brains of rats treated with chlorpromazine has been reported by Piha, Oja, and Usitalio (1) and by Glasky (2). In agreement with these observations, we were able to inhibit the incorporation of labeled amino acids into the brain proteins of mice by treating the animals with chlorpromazine. However, we were unable to demonstrate inhibition of the incorporation in vitro of the amino acids into the proteins of brain microsomes by chlorpromazine. Since chlorpromazine is known to interfere with temperature regulation in small animals (3), the relationship of body temperature to the effect of chlorpromazine on protein synthesis was investigated. The results presented in this paper indicate that chlorpromazine inhibits the incorporation of histidine and other amino acids into the proteins of various mouse tissues indirectly, by lowering body temperature. Several other changes produced by chlorpromazine can also be attributed to a lowered body temperature. These are a decreased rate of the disappearance of injected amino acids from the tissues, and the persistence of high levels of nicotinamide adenine dinucleotide in the liver following the injection of nicotinamide.