Acute Toxicity of Three New Selective COMT Inhibitors in Mice with Special Emphasis on Interactions with Drugs Increasing Catecholaminergic Neurotransmission

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Abstract
3‐Nitropyrocatechols are very potent and selective inhibitors of catechol‐O‐methyltransferase (COMT). LD50 values of three of these compounds were assessed after intraperitoneal administration with a special emphasis on interactions with drugs increasing catecholaminergic neurotransmission. LD50 values of the inhibitors varied from 137 mg/kg (Ro 41–0960. to 507 mg/kg (OR‐462) and 544 mg/kg (OR‐611). The LD50 value of Ro 41–096. was significantly lower than that of OR‐462 and OR‐611 (P<0.05). At toxic dose levels all inhibitors caused convulsions and hypomotility. OR‐462 and OR‐611 had statistically significant mortality increasing interaction with 20 mg/kg of nomifensine (P<0.05) and the former also with 10 mg/kg of amphetamine (P<0.05). Owing to their high therapeutic indexes these compounds can be considered useful new tools in pharmacological research.