Neurolepticlike actions of l-methadone: effect on mescaline-induced altered behavior and on tissue levels of mescaline in mice.

Mice were injected ip with either saline, l-methadone (2.5, 5, 20 mg/kg), perphenazine (1, 10, 15 mg/kg), or chlorprothixene (1.25, 2.5, 15 mg/kg) 30 min prior to mescaline-14C (25 mg/kg). Mescaline-induced behavioral changes such as agitation, excitement, slight increase in ventilation, and fright to sound stimuli were prevented by all doses of three drugs, and head-shaking, scratching, and locomotor-increasing effects by 5 and 20 mg/kg methadone and by all doses of both neuroleptics. Catalepticlike state and moderate to marked hypothermia induced by all doses of chlorprothixene, 10 and 15 mg/kg perphenazine, and 20 mg/kg methadone were not reversed by mescaline. Chlorprothixene (all doses), perphenazine (10, 15 mg/kg), and methadone (5, 20 mg/kg) caused marked retention of mescaline and its deaminated metabolite, 3, 4, 5-trimethoxyphenyl acetic acid in both brain and plasma. The fact that relatively higher doses of methadone than neuroleptics are needed to ensure effective antagonism to mescaline action tends to indicate a less specific interaction of the opiate with the neuroleptic/dopamine receptor proposed for central mescaline effects.