Pharmacologic Study of Psychotropic Drugs (I Report)

Interference of Tofanil, Chlorpromazine, Dimethylaminoethanol γ-Aminobutyric acid(GABA) with Pentobarbital Anesthesia

Abstract

The acute toxic actions of tofranil, chlorpromazine, dimethylaminoethanol and GABA injected intraperitoneally were examined on behaviour of mouse and the influences of the subtoxic doses of these psychotropic drugs on pentobarbital anesthesia were studied with mice.
1) The LD₅₀ of tofranil was 1.025mg per 10g body weight of mouse. After large doses of the drug, central excitatory symptoms occured and walking movement was observed as one of the severe toxic symptoms. But dimethylaminoethanol produced little change in behaviour when administered in doses of 5 to 20mg per 10g of body weight and the excitatory symptom was seen after 30mg of the drug which was near the lethal dose in mice. The effect of GABA on behaviour of mouse was scarcely observed even after 30mg of the drug.
2) Pentobarbital anesthesia was influenced by the small dose of tofranil, dimethylaminoethanol as well as GABA and the duration of pentobarbital anesthesia was shortened after the administration of each drug. In contrast with the effects of these drugs, chlorpromazine acted to prolong the duration of pentobarbital anesthesia.
3) The potentiation of pentobarbital anesthesia by chlorpromazine was completely depressed by the administration of small dose of tofranil. The above described suppression of pentobarbital anesthesia by dimethylaminoethanol or by GABA was diminished by the administration of small dose of tofranil.
4) On mechanism of central action of tofranil, dimethylaminoethanol as well as GABA, some discussions were done in reference to the effects of drugs on central limbic system and thalamic nuclei.