Tachyphylaxis to the antitetanus activity of some phenothiazine compounds.

Although chlorpromazine and acepromazine were the most potent suppressants of local tetanus induced in rabbits by intramuscular injection of the toxin of Cl. tetani, repeated injections lost their effect (tachyphylaxis) and sometimes even increased muscle activity, as did single large injections of either of the two drugs. As neither tachyphylaxis nor stimulation occurred in spinal animals, these effects might arise from an action in the brain-stem reticular formation on which chlorpromazine has been shown to have both inhibitory and excitatory effects. The possible cause of the tachyphylaxis is discussed. Evidence is advanced to support the view that tachyphylaxis can occur when chlorpromazine is used in the treatment of tetanus in man. Methotrimeprazine was more potent than chlorpromazine, but less prone to induce tachyphylaxis. These qualities rendered it more desirable for clinical use than the other two compounds.