Protein targets for drugs
Roger Mcfadden in Introducing Pharmacology, 2009
This chapter examines the physiological basis of mental health problems and neurological disorders and the action of the major drug groups used in the treatment of these problems. Many mental health drugs seem to exert their effects on the sections of the brain that control emotions and feelings. Drugs acting on the synapses of the brain do so in a variety of ways, but essentially, by various means they tend either to potentiate or to attenuate the action of a particular neurotransmitter. Antipsychotic drugs have a tranquilising and sedative effect on the mind and are used selectively for serious problems such as schizophrenia, severe anxiety and violent or unpredictably impulsive behaviour. The COMT inhibiting drugs such as entacapone and tolcapone prevents the degradation of levodopa outside the CNS. The chapter relates to the physiological pathologies that affect the brain and often result in psychological disorders that may edge them towards the category of mental health problems.
LEVODOPA
Neil Shear in Litt's Drug Eruption & Reaction Manual 25E, 2019
Synonyms: L-dopa; carbidopa Trade names: Duopa (Abbvie), Rytary (Impax), Sinemet (Bristol-Myers Squibb), Stalevo (Orion) Indications: Parkinsonism Class: Dopamine precursor Half-life: 1-3 hours Clinically important, potentially hazardous interactions with: ACE inhibitors, acebutolol, alfuzosin, alpha blockers, amisulpride, ampicillin, angiotensin II receptor antagonists, antihypertensives, antimuscarinics, antipsychotics, baclofen, benzodiazepines, beta blockers, bupropion, calcium channel blockers, captopril, chloramphenicol, cholestyramine, cilazapril, clobazam, clonidine, darifenacin, diazoxide, diuretics, dopamine D2 receptor antagonists, enalapril, erythromycin, fosinopril, hydralazine, irbesartan, iron salts, isoniazid, levomepromazine, linezolid, lisinopril, MAO inhibitors, memantine, methyldopa, metoclopramide, minoxidil, moclobemide, moxonidine, nitrates, olanzapine, olmesartan, oral iron, oxybutynin, paliperidone, papaverine, pericyazine, phenelzine, phenytoin, probenecid, pyridoxine, quetiapine, quinapril, ramipril, rifampin, risperidone, sapropterin, selegiline, sodium nitroprusside, sulpiride, tetrabenazine, tiotropium, trandolapril, tranylcypromine, tricyclic antidepressants, trospium, volatile liquid general anesthetics, ziprasidone, zuclopenthixol, zuclopenthixol acetate, zuclopenthixol decanoate, zuclopenthixol dihydrochloride Pregnancy category: C Important contra-indications noted in the prescribing guidelines for: nursing mothers; pediatric patients Note: Levodopa is always used in conjuntion with carbidopa. Stalevo is levodopa, carbidopa and entacapone. Contra-indicated in patients with narrow-angle glaucoma or those with a history of melanoma.
Potential benefit of entacapone for cocaine addiction: two case reports
Published in Journal of Substance Use, 2016
Nuno Rodrigues-Silva, Carlos Vasconcelos
Background: Entacapone is a COMT inhibitor approved for the treatment of Parkinson’s disease. Due to its selective action over prefrontal dopamine availability, it can be a viable alternative to reduce craving for several substances of abuse. We report two cases of cocaine addiction in which entacapone was initiated and produced beneficial effects with good tolerability. Case descriptions: The first patient abused cocaine for the past 2 years, with an average of two daily doses. He was also diagnosed with psychosis not otherwise specified 1 year before. The second patient was on treatment substitution program with methadone and abused cocaine for the past 15 years, with a present daily use of four doses. For both patients, despite psychological therapy they maintained daily cocaine abuse. Entacapone 200 mg was initiated 4tid, with the possibility for an increase to 400 mg 4tid. Over the following 4 weeks, patients were assessed every week: self-reported number of cocaine weekly doses; EMIT urine assays for cocaine; perceived craving, self-control; and cocaine effect. Conclusions: Self-reported consumption of cocaine reduced as well as the number of positive EMIT urine assays and perceived craving, while perceived self-control increased. This is the first study reporting the use of a COMT inhibitor for cocaine addiction. Despite the positive results, no recommendations can be made regarding the use of entacapone for cocaine addiction. However, this should raise interest to the potential benefit of a new drug class for cocaine addiction and motivate further studies with larger samples and improved methodological quality.
Clinical experience with the novel levodopa formulation entacapone + levodopa + carbidopa (Stalevo®)
Published in Expert Review of Neurotherapeutics, 2004
Levodopa is the main pharmacologic treatment for Parkinson’s disease. However, the long-term administration of levodopa is associated with the development of motor complications which can seriously compromise patient function. Increasing evidence indicates that such problems are related to abnormal pulsatile stimulation of striatal dopamine receptors and that treatments providing more continuous stimulation reduce the risk of motor complications. It is possible that administering levodopa with a reversible catechol-O-methyl transferase inhibitor at frequent intervals might reduce the risk of these complications. Stalevo® (Orion) combines levodopa, the dopa-decarboxylase inhibitor carbidopa and the catechol-O-methyl transferase inhibitor entacapone in a single tablet. This review provides an overview of the initial clinical experience gained with Stalevo during clinical trials, including several case studies.
Optimizing levodopa therapy to treat wearing-off symptoms in Parkinson’s disease: focus on levodopa/carbidopa/entacapone
Published in Expert Review of Neurotherapeutics, 2012
Levodopa has been the mainstay of Parkinson’s disease (PD) therapy for over 40 years, with its efficacy surpassing that of other antiparkinsonian medications. As such, most PD patients eventually require levodopa-based therapy during the course of the disease. However, despite its proven efficacy, long-term levodopa therapy is associated with motor complications, with wearing-off being the most prevalent. Wearing-off occurs, in part, as a result of the short half-life of levodopa, which leads to fluctuations in plasma levodopa levels. A pharmacokinetic profile characterized by a higher trough value of levodopa can be achieved by combining levodopa/carbidopa with entacapone, which inhibits the peripheral breakdown of levodopa, resulting in higher plasma levodopa levels. Here, we review the limitations of conventional levodopa and the clinical data for levodopa/carbidopa/entacapone in treating patients with wearing-off.
Related Knowledge Centers
- Inn
- Drug
- Comt Inhibitor
- Parkinson's Disease
- L-Dopa
- Blood – Brain Barrier
- Dopamine