Introduction Drugs containing imidazoline moieties, such as metronida- zole (MTZ), interact with specific imidazoline binding sites (IBS), of which two subtypes are known. While I 1 BS are involved in the regulation of blood pressure, the function of I 2 BS is not yet clear, but a regulatory effect on monoamine oxidase (MAO) activity has been described [1]. The mechanism responsible for the neurotoxic effects of MTZ, including dizziness, vertigo, headache and, very rarely, convulsions, incoordination and ataxia [2], is still unknown and we speculate that they could be caused by MAO inhibi- tion, as suggested by the partly similar neurotoxic profile of MAO inhibitors. Thus, we studied the effect of MTZ (0–10 –2 M) on bovine brain MAO using fluorimetric method with tyramine as the substrate [3]. Materials and methods Preparation of MAO Bovine brain mitochondria were isolated according to Basford [4] and stored at – 20 °C. The protein concentration of the mitochondrial fractions was determined by the Biuret method using a Perkin-Elmer l 9 spectrophotometer. Determination of MAO activity MAO activity was measured fluorimetrically using the method of Matsumoto et al. [3]. Briefly, the incubation mixtures contained: 0.1 ml of 0.25 M potassium phosphate buffer (pH 7.5); 0.1 ml of peroxidase solution (0.5 mg/ml); 0.1 ml of homovanillic acid solution (1 mg/ml); 0.1 ml of sample (mitochondria, 6 mg protein/ml), or water for the H 2 O 2 assay; 0.1 ml of tyramine at four final concentrations ranging from 10 –5 M to 10 –3 M or H 2 O 2 (22 nmoles/ml) and 0.1 ml of water; 0.05 ml of MTZ solution to give the final concentrations from 0 to 10 –2 M. The solutions were incubated for 30 min at 37 °C before stopping the reaction by addition of 2 ml of 0.1 M NaOH and the samples analyzed using a Perkin-Elmer LS 50B spectrofluorimeter. Inflamm. res. 50, Supplement 2 (2001) S 136 – S 137 1023-3830/01/02S136-02 $ 1.50+0.20/0 © Birkhäuser Verlag, Basel, 2001 Inflammation Research Inhibition of monoamine oxidase by metronidazole O. Befani 1 , E. Grippa 2 , L. Saso 2 , P. Turini 1 and B. Mondovì 1 1 Department of Biochemical Sciences “A. Rossi Fanelli”, C.N.R. Center of Molecular Biology, University of Rome “La Sapienza”, P. le Aldo Moro 5, 00185 Rome, Italy 2 Department of Pharmacology Natural Substances and General Physiology, University of Rome “La Sapienza”, P. le Aldo Moro 5, 00185 Rome, Italy, Fax: +39-6-49912480, e-mail: Eleonora.grippa@uniroma1.it Correspondence to: E. Grippa Fig. 1. MAO inhibition by metronidazole (A) Data are means ± SD of two experiments, each performed in duplicate. (B) Lineweaver-Burk plots in the presence of metronidazole at different concentrations ( = 0;  = 10 –5 M;  = 5 ¥ 10 –5 M;  = 10 –4 M); V = units of fluo- escence.