benztropine and Parkinson-Disease

The development of pharmacogenetic-based clinical practice guidelines for the use of anti-Parkinson's disease drugs requires, as a pre-requisite, the identification and validation of genetic biomarkers. These biomarkers are then used as surrogate endpoints. This review analyzes potential genetic biomarkers which can be used to improve anti-Parkinson's disease therapy.. The authors present an overview of current knowledge of pharmacogenetic implications of anti-Parkinson's disease drugs, including genes coding for the corresponding drug-metabolizing enzymes and drug targets. The gene/drug pairings with the strongest potential for pharmacogenetic recommendations include: CYP2C19/benztropine, COMT/levodopa and entacapone, CYP2B6/selegiline, UGT1A/entacapone, DRD2/ropinirole, pramipexole and cabergoline, and DRD3/ropinirole and pramipexole. Evidence supporting the effect of substrates, inhibitor or inducers for drug specific metabolizing enzymes in anti-Parkinson's disease drug response includes CYP1A2 in the response to ropinirole and rasagiline, and CYP3A4 in the response to bromocriptine, lisuride, pergolide and cabergoline. The authors present and discuss the current information on gene variations according to the 1000 genomes catalog and other databases with regards to anti-Parkinson's disease drugs. They also review and discuss the clinical implications of these variations.. The goal of pharmacogenomic testing for anti-Parkinson's disease drugs should be conservative and aimed at selecting determined drugs for determined patients. However, much additional research is still needed to obtain reliable pre-prescription tests.

Topics: Aryl Hydrocarbon Hydroxylases; Benzothiazoles; Benztropine; Bromocriptine; Cabergoline; Catechols; Cytochrome P-450 CYP1A2; Cytochrome P-450 CYP1A2 Inhibitors; Cytochrome P-450 CYP2B6; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP3A; Ergolines; Genetic Markers; Humans; Indans; Indoles; Levodopa; Lisuride; Nitriles; Parkinson Disease; Pergolide; Pharmacogenetics; Pramipexole; Receptors, Dopamine D2; Receptors, Dopamine D3; Reproducibility of Results; Selegiline

Topics: Animals; Basal Ganglia Diseases; Benztropine; Brain; Cats; Caudate Nucleus; Cerebellar Nuclei; Chlorpromazine; Corpus Striatum; Disease Models, Animal; Dopamine; Haloperidol; Haplorhini; Humans; Levodopa; Movement Disorders; Olivary Nucleus; Parkinson Disease; Putamen; Rats; Red Nucleus; Substantia Nigra; Thalamic Nuclei; Tremor

Topics: 5-Hydroxytryptophan; Amantadine; Anticonvulsants; Apomorphine; Benztropine; Carboxy-Lyases; Chemical Phenomena; Chemistry; Dihydroxyphenylalanine; Humans; Parasympatholytics; Parkinson Disease; Procyclidine; Trihexyphenidyl

Topics: Adult; Aged; Amantadine; Benztropine; Dihydroxyphenylalanine; Dopamine; Drug Synergism; Female; Humans; Hydrazines; Male; Middle Aged; Parasympatholytics; Parkinson Disease; Physical Therapy Modalities; Psychotherapy; Stereotaxic Techniques; Thalamus; Thinking

Four open-label studies have reported beneficial effects of clozapine on the tremor of idiopathic Parkinson's disease (PD). We performed a double-blind crossover trial with a 2-week washout, comparing low-dose clozapine to benztropine for the treatment of tremor in PD. Twenty-two subjects enrolled and 19 completed the study. Benztropine and clozapine were equally effective in improving tremor and the motor score of the United Parkinson's Disease Rating Scale at mean doses of 3.0 and 39 mg/day, respectively. Significant adverse events were experienced with each drug, but leukopenia was not encountered. We conclude that the atypical antipsychotic drug clozapine is helpful in the treatment of tremor in PD and should be considered when all other drug therapies fail.

Topics: Adult; Aged; Aged, 80 and over; Antiparkinson Agents; Antipsychotic Agents; Benztropine; Clozapine; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Middle Aged; Parkinson Disease; Treatment Outcome; Tremor

1. A randomized, placebo controlled, double-blind cross-over study was conducted to evaluate the clinical efficacy of the anticholinergic agent, benztropine mesylate (CogentinR) in 29 patients with mild to moderate, idiopathic Parkinson disease. 2. Patients were maintained on a stable, therapeutically optimal dosage and schedule of levadopa-carbidopa (Sinemet) throughout the study. 3. Both the neurologist's and the patient's global assessments of treatment efficacy indicated that Sinemet plus benztropine mesylate resulted in significantly greater improvement than Sinemet plus placebo. 4. Qualitative and quantitative evaluations of relevant neurologic functions showed small, but statistically significant improvements for rigidity, finger tapping speed and activities of daily living in patients during the Sinemet plus benztropine mesylate treatment period. 5. At the completion of the study 16 patients chose to continue taking benztropine mesylate as an adjuvant to Sinemet. 6. No important adverse side effects occurred during the study.

Topics: Aged; Antiparkinson Agents; Benztropine; Carbidopa; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Humans; Levodopa; Middle Aged; Parkinson Disease; Tropanes

A double-blind, placebo-controlled, crossover study with long-term follow-up of amantadien i- Parkinson's disease was performed on 26 patients. Other antiparkinsonian medications were discontinued in all but three patients. Amantadine resulted in a statistically significant 12 percent overall improvement over placebo. Twenty of 26 patients, without breaking the code, selected amantadine for long-term usage. Ten patients continued treatment for 10 to 12 months, and an overall statistically significant improvement was noted at 2 weeks and at 1, 2, 3, and 10 to 12 months. Improvements in tremor and rigidity remained relatively constant, while there was some apparent loss of efficacy in timed tests and quality of timed tests. Amantadine appears effective in the long-term treatment of some patients with Parkinson's disease.

Topics: Activities of Daily Living; Aged; Amantadine; Benztropine; Clinical Trials as Topic; Diphenhydramine; Drug Evaluation; Female; Follow-Up Studies; Humans; Locomotion; Long-Term Care; Male; Middle Aged; Muscle Rigidity; Parkinson Disease; Procyclidine; Time Factors; Tremor; Trihexyphenidyl

Topics: Administration, Oral; Amantadine; Antiparkinson Agents; Benztropine; Capsules; Chlorpromazine; Clinical Trials as Topic; Humans; Parkinson Disease; Parkinson Disease, Secondary; Placebos; Schizophrenia; Time Factors

Topics: Adult; Aged; Amantadine; Aromatic Amino Acid Decarboxylase Inhibitors; Benztropine; Dihydroxyphenylalanine; Dopamine; Evaluation Studies as Topic; Female; Homovanillic Acid; Humans; Hydroxyindoleacetic Acid; Male; Middle Aged; Muscle Rigidity; Parkinson Disease; Piperazines; Placebos; Probenecid; Pyrimidines; Receptors, Cholinergic; Tremor; Trihexyphenidyl

Topics: Adult; Amantadine; Basal Ganglia Diseases; Benztropine; Clinical Trials as Topic; Female; Humans; Male; Middle Aged; Movement Disorders; Parkinson Disease; Placebos

Topics: Aged; Benztropine; Brain; Clinical Trials as Topic; Depression; Dihydroxyphenylalanine; Evaluation Studies as Topic; Fatigue; Female; Fenclonine; Humans; Male; Mental Disorders; Middle Aged; Nausea; Parkinson Disease; Placebos; Serotonin; Sleep Initiation and Maintenance Disorders

Hereditary spastic paraplegia with thin corpus callosum is a rare degenerative disease, which is characterized by a progressive weakness of the lower limbs with a hypoplastic corpus callosum, and is often associated with other symptoms such as mental impairment, amyotrophy, sensory disturbances, dysuria, nystagmus and cataract. We describe two siblings (brother and sister) who showed a thin corpus callosum on MRI, one of whom showed the pure form of progressive spastic paraplegia, while the other showed predominant levodopa-responsive parkinsonism. The present cases are illustrative of a phenotypic heterogeneity in the same family of spastic paraplegia with a thin corpus callosum, despite the identical neuroimaging findings, and also presented another form of autosomal recessive juvenile levodopa-responsive parkinsonism.

Topics: Adolescent; Antiparkinson Agents; Benztropine; Cognition Disorders; Corpus Callosum; Electroencephalography; Female; Gait Disorders, Neurologic; Humans; Levodopa; Magnetic Resonance Imaging; Male; Muscle Weakness; Neuropsychological Tests; Parkinson Disease; Selegiline; Spastic Paraplegia, Hereditary; Tremor

Topics: Aged; Airway Obstruction; Antiparkinson Agents; Benztropine; Humans; Male; Parkinson Disease

Depression is commonly associated with idiopathic Parkinson's disease. Various antidepressants can be helpful in the treatment of this type of depression. Anticholinergic medications are at times used for treating the motor symptoms of parkinsonism. While some authors have reported euphorigenic effects from anticholinergics in other groups of patients, generally, they have not been used in the treatment of depression, with or without parkinsonism. In the case presented, a depressed patient with Parkinson's disease on levodopa/carbidopa and fluoxetine was given benztropine for his motor symptoms. The result was some improvement in his motor symptoms and a wide, dose-related spectrum of other central nervous system changes ranging from delirium to mania, hypomania, and euthymia from a "baseline" of residual depression. At a very low dose (0.25 mg per day), benztropine appeared to have an augmenting antidepressant effect that rendered the patient euthymic.

Topics: Aged; Benztropine; Carbidopa; Depressive Disorder; Dose-Response Relationship, Drug; Drug Therapy, Combination; Fluoxetine; Humans; Levodopa; Male; Parkinson Disease; Treatment Outcome

The importance of considering organic diseases when evaluating catatonic patients is illustrated by two cases of akinetic parkinsonism in which the patients became catatonic, with waxy flexibility. The catatonic syndrome occurs in association with a variety of lesions that may affect any level of the central nervous system from the brain stem to the cerebral hemispheres. A review of Parkinson's disease and a critical reappraisal of the catatonic syndrome are presented.

Topics: Adult; Akinetic Mutism; Benztropine; Carbidopa; Catatonia; Humans; Levodopa; Male; Parasympatholytics; Parkinson Disease; Syndrome

Three patients with progressive supranuclear palsy demonstrated atrophy of the midbrain, pons, cerebellum, and cerebral hemispheres by computed tomography with horizontal, sagittal, and coronal reconstruction. Benztropine therapy resulted in improvement of speech and gait without significantly affecting the vertical gaze palsy.

Topics: Aged; Atrophy; Basal Ganglia Diseases; Benztropine; Cerebellum; Eye Movements; Humans; Levodopa; Male; Mesencephalon; Middle Aged; Parkinson Disease; Speech; Tomography, X-Ray Computed; Tropanes

The effects of chronic administration of the anticholinergic agent, benztropine mesylate (CogentinTM), on specific verbal memory were investigated as part of a placebo-controlled randomized double-blind crossover study to determine the clinical efficiency of CogentinTM as an adjuvant therapy with SinemetTM in Parkinson's disease. Twenty-nine males with clinically definite idiopathic Parkinson's disease participated in the trial. They were tested for acquisition of new word lists, and on four other cognitive tests before, during, between, and after two 10-week trial periods when they received either increasing doses of CogentinTM (maximum 2 mg) or placebo while on a maintenance dose of SinemetTM. Patients showed a statistically significant decrease (5--10%) in word list acquisition while on CogentinTM. The anticholinergic memory effect was unrelated to the degree of improved clinical efficacy of CogentinTM for the Parkinsonism, and to initial word list acquisition ability. Verbal memory findings indicate that chronic administration of an anticholinergic in even low therapeutic dosage may play an important role in memory function.

Topics: Aged; Benztropine; Double-Blind Method; Humans; Male; Memory; Mental Recall; Middle Aged; Parkinson Disease; Tropanes; Verbal Learning

Topics: Amantadine; Benztropine; Humans; Levodopa; Parkinson Disease; Procyclidine; Trihexyphenidyl

Topics: Acetylcholine; Basal Ganglia Diseases; Benztropine; Corpus Striatum; Dopamine; Fluphenazine; Haloperidol; Humans; Levodopa; Models, Neurological; Movement Disorders; Parkinson Disease; Reserpine; Schizophrenia; Tranquilizing Agents; Trihexyphenidyl

Topics: Amantadine; Benztropine; Biperiden; Humans; Levodopa; Orphenadrine; Parkinson Disease; Procyclidine; Trihexyphenidyl

In 13 elderly patients, 12 of whom had Parkinson's disease, visual hallucinations and delirium developed as a side effect of amantadine hydrochloride (Symmetrel) therapy. The symptoms promptly disappearred when amantadine was discontinued. Thereafter, each parkinsonian patient was treated satisfactorily with levo-dopa. Treatment with a combination of amantadine and an anticholinergic agent increases the likelihood of delirium because of the hazard of retention of urine. Although amantadine is effective in the treatment of Parkinson's disease in the elderly, the incidence of delirium as a complication seems higher in this age group.

Topics: Aged; Amantadine; Benztropine; Biperiden; Delirium; Drug Eruptions; Female; Hallucinations; Humans; Levodopa; Male; Middle Aged; Orphenadrine; Parkinson Disease

Twelve parkinsonian patients on long-term levodopa therapy developed intermittent, myoclonic body jerks. The movements consisted of single unilateral or bilateral abrupt jerks of the extremities and occurred most frequently during sleep. Although directly related to daily dosage of levodopa, the myoclonus was specifically blocked by the serotonin antagonist, methysergide. Levodopa-induced myoclonus may be related to intermittent increases of activity of serotonin in the brain and results from levodopa-induced dysregulation of serotonin activity.

Topics: 5-Hydroxytryptophan; Aged; Amantadine; Amphetamine; Animals; Benztropine; Dopamine Antagonists; Dose-Response Relationship, Drug; Female; Guinea Pigs; Humans; Levodopa; Male; Methysergide; Middle Aged; Movement Disorders; Myoclonus; Parkinson Disease; Propranolol; Serotonin; Serotonin Antagonists; Sleep; Trihexyphenidyl

Topics: Aged; Benztropine; Biperiden; Electromyography; Female; Humans; Male; Middle Aged; Movement Disorders; Parasympatholytics; Parkinson Disease; Phenothiazines; Procyclidine; Trihexyphenidyl

Topics: Aged; Aromatic Amino Acid Decarboxylase Inhibitors; Benztropine; Carbidopa; Dihydroxyphenylalanine; Dopamine; Drug Synergism; Evaluation Studies as Topic; Female; Humans; Male; Middle Aged; Parkinson Disease; Pyridoxine; Spinal Puncture; Trihexyphenidyl

Topics: Animals; Atropine; Benztropine; Butyrophenones; Cats; Chlorpromazine; Dose-Response Relationship, Drug; Electromyography; Motor Neurons; Parkinson Disease; Parkinson Disease, Secondary; Phenothiazines; Rabbits; Rats; Reserpine; Tetanus; Time Factors; Tremorine; Trifluoperazine

Topics: Animals; Basal Ganglia Diseases; Benztropine; Carbon Isotopes; Chromatography, Thin Layer; Feces; Female; Fluphenazine; Half-Life; Haplorhini; Papio; Parkinson Disease; Parkinson Disease, Secondary; Trihexyphenidyl

Topics: Benztropine; Humans; Parasympatholytics; Parkinson Disease; Parkinsonian Disorders

Topics: Benztropine; Cardiovascular Agents; Muscle Relaxants, Central; Parkinson Disease; Parkinsonian Disorders

Topics: Benztropine; Cardiovascular Agents; Mesylates; Muscle Relaxants, Central; Parkinson Disease

Topics: Benztropine; Cardiovascular Agents; Mesylates; Muscle Relaxants, Central; Parkinson Disease; Parkinsonian Disorders