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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Acute toxicity of three new selective COMT inhibitors in mice with special emphasis on interactions with drugs increasing catecholaminergic neurotransmission.

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 41-0960 was significantly lower than that of OR-462 and OR-611 (P less than 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 less than 0.05) and the former also with 10 mg/kg of amphetamine (P less than 0.05). Owing to their high therapeutic indexes these compounds can be considered useful new tools in pharmacological research.[1]

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