The role of physicochemical properties of entacapone and tolcapone on their efficacy during local intrastriatal administration

Forsberg, Markus; Huotari, Marko; Savolainen, Jouko; Männistö, Pekka T.

doi:10.1016/j.ejps.2005.01.005

Cited by 23 publications

(22 citation statements)

References 28 publications

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“…The concentration of MDMA in the perfusate was chosen based upon previous studies showing that the extracellular concentration of MDMA under these experimental conditions is similar to that found after systemic neurotoxic doses of MDMA (Esteban et al 2001;Nixdorf et al 2001;Breier et al 2006). On the other hand, the concentration of entacapone in the perfusate was chosen based upon a previous study showing an effective inhibition of brain COMT activity (Forsberg et al 2005).…”

Section: Reverse Dialysis Studiesmentioning

confidence: 99%

The relationship between core body temperature and 3,4-methylenedioxymethamphetamine metabolism in rats: implications for neurotoxicity

et al. 2007

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Section: Reverse Dialysis Studiesmentioning

confidence: 99%

The relationship between core body temperature and 3,4-methylenedioxymethamphetamine metabolism in rats: implications for neurotoxicity

et al. 2007

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“…Indeed, several studies have shown that after systemic administration, 3 penetrates better into the brain than 1 and 2 [6] [7]. The brain COMT inhibition observed with 1 is lower and obtained at higher doses, while 2 is only peripherally active [5].…”

mentioning

confidence: 99%

The Lipophilicity Behavior of Three Catechol-O-methyltransferase (COMT) Inhibitors and Simple Analogues

Novaroli

Doulakas

Reist

et al. 2006

HCA

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The ionization and lipophilicity properties of the second-generation catechol-O-methyltransferase (COMT) inhibitors entacapone (1), nitecapone (2), and tolcapone (3) which share the same nitrocatechol structure but have remarkably different pharmacokinetic profiles are investigated to identify relationships between some of these physicochemical parameters and the blood-brain-barrier (BBB) passage. In addition, the lipophilicity behavior of the simpler, structurally related analogues 4 -11 is studied. Combined descriptors such as Dlog P (difference between log P in two different solvent systems) and diff(log P NÀI ) (difference between log P of two different electrical forms of a given solute in the same system) provide insight into inter-and intramolecular interactions characteristic of the analyzed compounds.

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“…However, COMT inhibition may also promote the synthesis of more basic LD metabolites, i.e., the tyrosine aminotransferase dependent substrates dihydroxyphenylpyruvate acetate and trihydroxyphenylacetate. Therefore COMT inhibition may model the environmental pH and the physicochemical properties of LD for its duodenal absorption, since this enzyme is located in higher concentrations in the membranes of the gastrointestinal tract 1–3. Generally, these physicochemical properties of a drug also affect its absorption through the gastrointestinal tract 2, 4.…”

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confidence: 99%

Entacapone improves absorption of a coadministered salt in patients with Parkinson's disease

et al. 2008

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Entacapone (EN) improves the efficacy of levodopa/dopadecarboxylase inhibitor (LD/DDI) formulations by inhibition of the enzyme catechol-O-methyltransferase (COMT). COMT inhibition also promotes the synthesis of basic LD metabolites, whereas DDI support the composition of acidic LD derivatives. LD metabolism correlates to the one of (13)C-sodium-octanoate, which is employed in breath tests to measure gastric emptying velocity. Objectives were to investigate the impact of COMT inhibition on the recovery rate of (13)C-sodium-octanoate in parkinsonian patients, who received first 100 mg LD/Carbidopa (CD) and the next day 100 mg LD/CD/EN combined with (13)C-sodium-octanoate in each case. The recovery rate of (13)C-sodium-octanoate was significant higher during the LD/CD/EN-compared with the LD/CD condition. COMT inhibition combined with LD/DDI improves absorption of a co-administered salt probably due to a COMT inhibition induced basic environment in gastrointestinal membranes. This improves dissolution and absorption of acids and salts. Thus it may enhance absorption of LD itself.

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The role of physicochemical properties of entacapone and tolcapone on their efficacy during local intrastriatal administration

Cited by 23 publications

References 28 publications

The relationship between core body temperature and 3,4-methylenedioxymethamphetamine metabolism in rats: implications for neurotoxicity

The relationship between core body temperature and 3,4-methylenedioxymethamphetamine metabolism in rats: implications for neurotoxicity

The Lipophilicity Behavior of Three Catechol-O-methyltransferase (COMT) Inhibitors and Simple Analogues

Entacapone improves absorption of a coadministered salt in patients with Parkinson's disease

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