Toxicity, mutagenicity, and behavioral effects of β-CIT, a ligand for dopamine transporter exploration by SPECT

被引:4
作者
Emond, P
Farde, L
Chalon, S
Belzung, C
Mauclaire, V
Chiron, JP
Halldin, C
Besnard, JC
Guilloteau, D
机构
[1] INSERM, U316, Lab Biophys Med & Pharmaceut, F-37200 Tours, France
[2] Karolinska Inst, Dept Clin Neurosci, Psychiat Sect, S-17176 Stockholm, Sweden
[3] LEPCO, Fac Sci, F-37200 Tours, France
[4] Cis Bio Ind, F-91192 Gif Sur Yvette, France
[5] ADREMI, Lab Microbiol Immunol, Fac Sci Pharmaceut Philippe Maupas, F-37200 Tours, France
关键词
dopamine; SPECT; beta-CIT; toxicity;
D O I
10.1016/S0969-8051(97)00227-8
中图分类号
R8 [特种医学]; R445 [影像诊断学];
学科分类号
1002 ; 100207 ; 1009 ;
摘要
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 mice and rats. The LD50 values were about 20 mg and 5 mg for mice and rats, respectively. There was no sex difference. The mutagenicity was evaluated using the Ames' test. No mutagenic effect was observed for beta-CIT. Effects on locomotor activity were measured in mice using the open-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 effect of beta-CIT at the dopamine transporter. We conclude that with no mutagenic effects and LD50 more than 6 orders of magnitude higher than the routinely used doses in PET or SPET, it can be assumed that beta-CIT can be safely used as a radioligand in humans. (C) 1998 Elsevier Science Inc.
引用
收藏
页码:405 / 409
页数:5
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