Catechol-O-methyltransferase inhibitor
[1] Entacapone and opicapone are peripherally selective inhibitors, unable to cross the blood–brain barrier (BBB), and hence do not inhibit COMT in the brain.[3] Instead, the drug seems to exert most of its clinical efficacy in this condition through inhibition of peripheral COMT and is dependent on concomitant use of levodopa.[8] Tolcapone, which acts centrally in addition to peripherally, has shown antidepressant-like effects in animal models of depression.[10] However, these antidepressant-like effects may only occur with combination treatment of tolcapone with levodopa and an aromatic L-amino acid decarboxylase inhibitor.[11] There may be compensatory activation of the monoamine oxidase dopamine-metabolizing pathway with brain COMT inhibition.
catechol-O-methyltransferasemethylatescatecholaminesdopaminenorepinephrineepinephrinelevodopaParkinson's diseasecombinationaromatic L-amino acid decarboxylase inhibitorcarbidopabenserazide3-O-methyldopabioavailabilitycarbidopa/levodopaEntacaponeOpicaponeTolcaponeNebicaponeNeluxicaponeNitecaponeperipherally selective inhibitorsblood–brain barrieracute liver failuredepressive disorderspreclinical researchantidepressantanimal modelsstriatumnucleus accumbensfrontal cortexmonoamine oxidasecarbidopa/levodopa/entacaponePharmacologyenzyme inhibitionCompetitive inhibitionUncompetitive inhibitionNon-competitive inhibitionSuicide inhibitionMixed inhibitionOxidoreductaseAldose reductaseHMG-CoA reductase5α-ReductaseDihydrofolate reductaseLipoxygenaseAromataseXanthine oxidaseRibonucleotide reductaseTransferaseThymidylate synthaseDihydropteroate synthetaseFarnesyltransferaseGABA transaminaseNucleotidyltransferaseIntegraseReverse transcriptaseProtein kinaseTyrosine kinaseJanus kinaseHydrolasePhosphodiesteraseAcetylcholinesteraseRibonucleasePolygalacturonaseNeuraminidaseAlpha-glucosidaseProteaseExopeptidaseEndopeptidaseTrypsinEnkephalinaseMatrix metalloproteinaseOxytocinaseHistone deacetylaseBeta-lactamaseDopa decarboxylaseCarbonic anhydraseSteroidogenesis inhibitorDopaminergicsprecursors+benserazide+carbidopa+carbidopa/entacaponeFoslevodopa+foscarbodipaMelevodopaDA receptoragonistsBromocriptineCabergolineDihydroergocryptineLisuridePergolideApomorphinePiribedilPramipexoleRopiniroleRotigotineTalipexoleinhibitorsRasagilineSafinamideSelegiline+levodopa+melevodopaFoscarbidopa+foslevodopaAnticholinergicsBenzatropineBiperidenBornaprineChlorphenoxamineCycrimineDexetimideDiphenhydramineEtanautineEtybenzatropineMazaticolMetixeneOrphenadrinePhenglutarimidePiroheptineProcyclidineProfenamineTigloidine