Analysis of information sources in references of the Wikipedia article "Catechol-O-methyltransferase inhibitor" in English language version.
CERC-406 and CERC-425: Residual Motoric and Cognitive Impairment. CERC-406 and CERC-425 are preclinical candidates from our proprietary platform of compounds that inhibit catechol-O-methyltransferase, or COMT, within the brain, which we refer to as our COMTi platform. We believe they may have the potential to be developed for the treatment of residual cognitive impairment symptoms such as Parkinson's disease.
The efficacy of tolcapone as an adjunct to levodopa in patients with Parkinson's disease has primarily been attributed to its ability to inhibit peripheral it is thought that tolcapone enters the CNS to a minimal extent only.[16] However, results [17] of a study in patients with Parkinson's disease, as well as results of animal studies,[18-21] suggest that tolcapone also has central activity.
Tolcapone is a potent, selective and reversible inhibitor of COMT in the periphery.8 It also exerts COMT inhibition in the brain, but the relevance of this effect to its efficacy in PD is less clear.9 [...] Although tolcapone has been shown to inhibit central COMT, its clinical efficacy seems to be mainly mediated through inhibition of peripheral COMT and depends on concomitant use of exogenous levodopa.17
In accord with its ability to enhance CNS catecholamine levels, tolcapone has been shown to possess antidepressant-like behavioral effect in a rat model of chronic stress with production of an anhedonic state produced by self-stimulation of the ventral tegmental area (Moreau et al. 1994), but others, using a standard chronic stress test, found that antidepressant effect appeared only with a combination of COMT-I, l-DOPA and AAADC-I treatment (Mannisto et al. 1995). Tolcapone, and potentially other CNS-active COMTI, could theoretically be useful in treatment of both depressive and motor symptoms of PD, but further developmental work is necessary to establish this joint treatment.
The efficacy of tolcapone as an adjunct to levodopa in patients with Parkinson's disease has primarily been attributed to its ability to inhibit peripheral it is thought that tolcapone enters the CNS to a minimal extent only.[16] However, results [17] of a study in patients with Parkinson's disease, as well as results of animal studies,[18-21] suggest that tolcapone also has central activity.
Tolcapone is a potent, selective and reversible inhibitor of COMT in the periphery.8 It also exerts COMT inhibition in the brain, but the relevance of this effect to its efficacy in PD is less clear.9 [...] Although tolcapone has been shown to inhibit central COMT, its clinical efficacy seems to be mainly mediated through inhibition of peripheral COMT and depends on concomitant use of exogenous levodopa.17
In accord with its ability to enhance CNS catecholamine levels, tolcapone has been shown to possess antidepressant-like behavioral effect in a rat model of chronic stress with production of an anhedonic state produced by self-stimulation of the ventral tegmental area (Moreau et al. 1994), but others, using a standard chronic stress test, found that antidepressant effect appeared only with a combination of COMT-I, l-DOPA and AAADC-I treatment (Mannisto et al. 1995). Tolcapone, and potentially other CNS-active COMTI, could theoretically be useful in treatment of both depressive and motor symptoms of PD, but further developmental work is necessary to establish this joint treatment.
Tolcapone is a potent, selective and reversible inhibitor of COMT in the periphery.8 It also exerts COMT inhibition in the brain, but the relevance of this effect to its efficacy in PD is less clear.9 [...] Although tolcapone has been shown to inhibit central COMT, its clinical efficacy seems to be mainly mediated through inhibition of peripheral COMT and depends on concomitant use of exogenous levodopa.17
