TOXICITY, MUTAGENICITY, AND BEHAVIORAL-EFFECTS OF BETA-CIT, A LIGAND FOR DOPAMINE TRANSPORTER EXPLORATION BY SPECT

The cocaine analog beta-CIT is one of the most used compounds for SPET examination of the dopamine transporter in drug abuse and Parkinson's disease. However, the toxicity of this agent has not yet been studied . We report here acute toxicity, mutagenicity, and effect on locomotor activity of beta-CIT. Acute toxicity experiments were performed in mi ce and rats. The LD50 values were about 20 mg and 5 mg for mice and ra ts, respectively. There was no sex difference. The mutagenicity was ev aluated using the Ames' test. No mutagenic effect was observed for bet a-CIT. Effects on locomotor activity were measured in mice using the o pen-field test. beta-CIT increased locomotion (+65%) when injected at a dose of 0.312 mg/kg; the maximal increase (+205%) was observed at a dose of 1.25 mg/kg; at higher doses, the effect was decreased slightly . These pharmacological findings are in agreement with an inhibitory e ffect of beta-CIT at the dopamine transporter. We conclude that with n o mutagenic effects and LD50 more than 6 orders of magnitude higher th an the routinely used doses in PET or SPET, it can be assumed that bet a-CIT can be safely used as a radioligand in humans. (C) 1998 Elsevier Science Inc.