Nebicapone

Nebicapone
Clinical data
Other names	BIA 3-202; 3-Nitro-5-phenylacetyl catechol
Drug class	Catechol O-methyltransferase inhibitor
Identifiers
	IUPAC name 1-(3,4-dihydroxy-5-nitrophenyl)-2-phenylethanone;
CAS Number	274925-86-9;
PubChem CID	9838389;
DrugBank	DB14849;
ChemSpider	8014109;
UNII	NM2KXJ990T;
ChEMBL	ChEMBL160038;
Chemical and physical data
Formula	C14H11NO5
Molar mass	273.244 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES C1=CC=C(C=C1)CC(=O)C2=CC(=C(C(=C2)O)O)[N+](=O)[O-];
	InChI InChI=1S/C14H11NO5/c16-12(6-9-4-2-1-3-5-9)10-7-11(15(19)20)14(18)13(17)8-10/h1-5,7-8,17-18H,6H2; Key:MRFOLGFFTUGAEB-UHFFFAOYSA-N;

Nebicapone (developmental code name BIA 3-202) is a catechol O-methyltransferase (COMT) inhibitor which was under development for the treatment of Parkinson's disease but was never marketed.^[1]^[2] It is a nitrocatechol and is structurally related to entacapone, nitecapone, and tolcapone.^[2] The drug shows peripheral selectivity and does not significantly act in the brain.^[2] In contrast to the centrally penetrant tolcapone, nebicapone does not potentiate the psychostimulant-like effects of amphetamine in animals.^[3]^[4] Nebicapone was found to be effective for Parkinson's disease in clinical trials.^[5] However, it also showed hepatotoxicity, including elevated liver enzymes.^[2]^[5]^[6] As a result, its development was discontinued by 2014.^[6] Nebicapone was first described in the scientific literature by 2000.^[7]^[8]

References

^ "Nebicapone: Uses, Interactions, Mechanism of Action". DrugBank Online. 20 May 2019. Retrieved 8 October 2024.
^ ^a ^b ^c ^d Haasio K (2010). "Toxicology and safety of COMT inhibitors". Int Rev Neurobiol. 95: 163–189. doi:10.1016/B978-0-12-381326-8.00007-7. PMID 21095462.
^ Guay DR (January 1999). "Tolcapone, a selective catechol-O-methyltransferase inhibitor for treatment of Parkinson's disease". Pharmacotherapy. 19 (1): 6–20. doi:10.1592/phco.19.1.6.30516. PMID 9917075. 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.
^ Parada A, Soares-da-Silva P (October 2000). "POSTER COMMUNICATIONS: 49P. BIA 3-202 does not potentiate locomotor hyperactivity during increased dopaminergic stimulation". British Journal of Pharmacology. 131 (Suppl). Wiley: 7. Retrieved 8 October 2024. 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.
^ ^a ^b Marsala SZ, Gioulis M, Ceravolo R, Tinazzi M (2012). "A systematic review of catechol-0-methyltransferase inhibitors: efficacy and safety in clinical practice". Clin Neuropharmacol. 35 (4): 185–190. doi:10.1097/WNF.0b013e31825c034a. PMID 22805229.
^ ^a ^b Kiss LE, Soares-da-Silva P (November 2014). "Medicinal chemistry of catechol O-methyltransferase (COMT) inhibitors and their therapeutic utility". J Med Chem. 57 (21): 8692–8717. doi:10.1021/jm500572b. PMID 25080080.
^ Vieira-Coelho, M. A., Borges, N., Parada, A., Learmonth, D. A., Benes, J., & Soares-da-Silva, P. (2000). ORAL COMMUNICATIONS-BIA 3-202, a long-acting catechol-O-methyltransferase inhibitor with limited brain access. British Journal of Pharmacology-Proceedings Supplement, 2-2. https://scholar.google.com/scholar?cluster=3859334956887569813
^ Parada A, Loureiro AI, Vieira-Coelho MA, Hainzl D, Soares-da-Silva P (May 2001). "BIA 3-202, a novel catechol-O-methyltransferase inhibitor, enhances the availability of L-DOPA to the brain and reduces its O-methylation". Eur J Pharmacol. 420 (1): 27–32. doi:10.1016/s0014-2999(01)01020-2.

[DrugBank-1] "Nebicapone: Uses, Interactions, Mechanism of Action". DrugBank Online. 20 May 2019. Retrieved 8 October 2024.

[Haasio2010-2] Haasio K (2010). "Toxicology and safety of COMT inhibitors". Int Rev Neurobiol. 95: 163–189. doi:10.1016/B978-0-12-381326-8.00007-7. PMID 21095462.

[Guay1999-3] Guay DR (January 1999). "Tolcapone, a selective catechol-O-methyltransferase inhibitor for treatment of Parkinson's disease". Pharmacotherapy. 19 (1): 6–20. doi:10.1592/phco.19.1.6.30516. PMID 9917075. 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.

[ParadaSoares-da-Silva2000-4] Parada A, Soares-da-Silva P (October 2000). "POSTER COMMUNICATIONS: 49P. BIA 3-202 does not potentiate locomotor hyperactivity during increased dopaminergic stimulation". British Journal of Pharmacology. 131 (Suppl). Wiley: 7. Retrieved 8 October 2024. 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.

[MarsalaGioulisCeravolo2012-5] Marsala SZ, Gioulis M, Ceravolo R, Tinazzi M (2012). "A systematic review of catechol-0-methyltransferase inhibitors: efficacy and safety in clinical practice". Clin Neuropharmacol. 35 (4): 185–190. doi:10.1097/WNF.0b013e31825c034a. PMID 22805229.

[KissSoares-da-Silva2014-6] Kiss LE, Soares-da-Silva P (November 2014). "Medicinal chemistry of catechol O-methyltransferase (COMT) inhibitors and their therapeutic utility". J Med Chem. 57 (21): 8692–8717. doi:10.1021/jm500572b. PMID 25080080.

[Vieira-CoelhoBorgesParada2000-7] Vieira-Coelho, M. A., Borges, N., Parada, A., Learmonth, D. A., Benes, J., & Soares-da-Silva, P. (2000). ORAL COMMUNICATIONS-BIA 3-202, a long-acting catechol-O-methyltransferase inhibitor with limited brain access. British Journal of Pharmacology-Proceedings Supplement, 2-2. https://scholar.google.com/scholar?cluster=3859334956887569813

[ParadaLoureiroVieira-Coelho2001-8] Parada A, Loureiro AI, Vieira-Coelho MA, Hainzl D, Soares-da-Silva P (May 2001). "BIA 3-202, a novel catechol-O-methyltransferase inhibitor, enhances the availability of L-DOPA to the brain and reduces its O-methylation". Eur J Pharmacol. 420 (1): 27–32. doi:10.1016/s0014-2999(01)01020-2.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]