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| Other names | BIA 3-202; 3-Nitro-5-phenylacetyl catechol |
| Drug class | CatecholO-methyltransferase inhibitor |
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| Formula | C14H11NO5 |
| Molar mass | 273.244 g·mol−1 |
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Nebicapone (developmental code nameBIA 3-202) is acatecholO-methyltransferase (COMT)inhibitor which was under development for the treatment ofParkinson's disease but was never marketed.[1][2] It is anitrocatechol and isstructurally related toentacapone,nitecapone, andtolcapone.[2] The drug showsperipheral selectivity and does not significantly act in thebrain.[2] In contrast to thecentrally penetrant tolcapone, nebicapone does not potentiate thepsychostimulant-like effects ofamphetamine in animals.[3][4] Nebicapone was found to be effective for Parkinson's disease inclinical trials.[5] However, it also showedhepatotoxicity, includingelevated liver enzymes.[2][5][6] As a result, its development was discontinued by 2014.[6] Nebicapone was first described in thescientific literature by 2000.[7][8]
It also enhances locomotor hyperactivity induced by amphetamine and nomifensine and stereotypy induced by amphetamine, and stimulates exploratory activity in the open field test in rats and mice.14 Tolcapone potentiates levodopa antagonism of haloperidol-induced catalepsy in MPP+-lesioned mice (murine model of Parkinson's disease) and potentiates and prolongs levodopa-induced circling behavior in rats with 6-hydroxydopamine-induced nigrostriatal pathway lesions (another animal model of Parkinson's disease).23, 24 [...] The effect of tolcapone on animal models of depression was evaluated in two studies. In rats with chronic mild stress-induced anhedonia, tolcapone 10 or 30 mg/kg twice/day by intraperitoneal injection prevented the stress-induced anhedonic state compared with vehicle-treated controls.28 Another rat study using the forced swimming test and learned helplessness paradigm, found no significant antidepressant activity of the agent.29 The relevance of these findings to the management of depression in humans with both parkinsonian and nonparkinsonian disease is unknown.
Tolcapone administered 6 h before amphetamine challenge was found to significantly increase locomotor activity in rats treated with 0.5 and 2.0 mg kg-1 amphetamine. In rats given 4.0 mg kg-1 amphetamine, tolcapone produced a marked decrease in locomotor activity and increased two-fold the duration of the stereotyped behaviour.
