piperidines and Chorea

Chorea is defined as jerk-like movements that move randomly from one body part to another. It is due to a variety of disorders and although current symptomatic therapy is quite effective there are few etiology- or pathogenesis-targeted therapies. The aim of this review is to summarize our own experience and published evidence in the treatment of chorea. Areas covered: After evaluating current guidelines and clinical practices for chorea of all etiologies, PubMed was searched for the most recent clinical trials and reviews using the term 'chorea' cross referenced with specific drug names. Expert commentary: Inhibitors of presynaptic vesicular monoamine transporter type 2 (VMAT2) that cause striatal dopamine depletion, such as tetrabenazine, deutetrabenazine, and valbenazine, are considered the treatment of choice in patients with chorea. Some clinicians also use dopamine receptor blockers (e.g. antipsychotics) and other drugs, including anti-epileptics and anti-glutamatargics. 'Dopamine stabilizers' such as pridopidine and other experimental drugs are currently being investigated in the treatment of chorea. Deep brain stimulation is usually reserved for patients with disabling chorea despite optimal medical therapy.

Topics: Antipsychotic Agents; Chorea; Deep Brain Stimulation; Dopamine Antagonists; Humans; Piperidines; Tetrabenazine; Transcranial Magnetic Stimulation; Valine; Vesicular Monoamine Transport Proteins

Striatal cholinergic dysfunction may be important in Huntington disease (HD). We studied whether donepezil improves chorea, cognition, and quality of life (QoL) in HD. Thirty patients were randomly assigned to treatment with donepezil or placebo. At the doses studied, donepezil did not improve chorea, cognition, or QoL. Adverse events were similar between both groups. Based on this small sample study, donepezil was not an effective treatment for HD.

Topics: Chorea; Cognition Disorders; Donepezil; Female; Humans; Huntington Disease; Indans; Male; Middle Aged; Nootropic Agents; Outcome Assessment, Health Care; Piperidines; Placebo Effect; Quality of Life; Recovery of Function; Treatment Outcome

Topics: Chorea; Humans; Piperidines

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Cholinesterase Inhibitors; Chorea; Donepezil; Humans; Indans; Magnetic Resonance Imaging; Male; Piperidines; Tomography, Emission-Computed, Single-Photon

Previously, enhanced levels of spermine which stimulates N-methyl-D-aspartate (NMDA) receptors, particularly those containing the NR2B subunit, were found in brains of dt(sz) mutant hamsters, a model of paroxysmal dyskinesia in which dystonic episodes occur in response to stress. Therefore, the effects of the NR2B selective NMDA receptor antagonist Ro 25-6981 ([R-(R,S)]-alpha-(4-hydroxyphenyl)-beta-methyl-4-phenyl-methyl)-1-piperidine-propanol] on severity of dystonia were investigated in the dt(sz) hamster. Ro 25-6981 failed to exert antidystonic effects, but even caused a moderate aggravation at higher doses (10.0, 12.5 mg/kg). This result indicates that overstimulation of receptors that include the NR2B subunit by polyamines is not involved in the dystonic syndrome. NR2B-selective NMDA receptor antagonists seem not to provide a novel approach in the treatment of hereditary paroxysmal dyskinesias.

Topics: Animals; Chorea; Cricetinae; Dose-Response Relationship, Drug; Locomotion; Mutation; Phenols; Piperidines; Receptors, N-Methyl-D-Aspartate; Severity of Illness Index; Time Factors

Previous studies suggested that glutamatergic overactivity contributes to the manifestation of dystonia in the dt(sz) mutant hamster, a model of idiopathic paroxysmal dyskinesia in which dystonic episodes occur in response to mild stress. Therefore, the role of polyamines, known as positive modulators of NMDA receptors, was examined in the present study. The levels of polyamines (putrescine, spermidine, spermine) were determined in forebrain, cerebellum and brainstem in dt(sz) hamsters at an age of most marked expression of dystonia (32 days) and in age-matched non-dystonic control hamsters. Spermine was found to be significantly increased in the forebrain (35%) of dystonic animals, while spermidine was unaltered in dystonic brains and only a moderate increase in putrescine (12%) was detected in the cerebellum of dt(sz) mutants. In view of enhanced spermine levels, the effect of the putative polyamine receptor antagonist ifenprodil on the severity of dystonia was examined in dystonic hamsters. Ifenprodil (5-40 mg/kg i.p.) failed to exert a beneficial effect, but even aggravated dystonia in the dt(sz) mutant at higher doses. These data together with previous pharmacological findings in mutant hamsters do not completely exclude a pathophysiological role of enhanced polyamine levels but suggest that overstimulation of NMDA receptors which contain NR2B subunits by enhanced spermine levels is not involved in the dystonic syndrome.

Topics: Aging; Animals; Brain; Case-Control Studies; Chorea; Cricetinae; Disease Models, Animal; Dose-Response Relationship, Drug; Dystonia; Excitatory Amino Acid Agents; Mutation; Piperidines; Polyamines; Receptors, N-Methyl-D-Aspartate; Severity of Illness Index

Previous studies have shown beneficial effects of the cannabinoid CB(1)/CB(2) receptor agonist (R)-4,5-dihydro-2-methyl-4-(4-morpholinylmethyl)-1-(1-naphthalenylcarbonyl)-6H-pyrrolo [3,2,1-ij]quinolin-6-one mesylate (WIN 55,212-2) in dt(sz) mutant hamsters, a model of idiopathic paroxysmal dystonia (dyskinesia). To examine the pathophysiological significance of the cannabinergic system in the dystonic syndrome, the effect of the cannabinoid CB(1) receptor antagonist N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-3-pyrazole-carboxamide (SR 141716A) on severity of dystonia was investigated in dt(sz) mutants which exhibit episodes of dystonic and choreoathetotic disturbances in response to mild stress. SR 141716A (5 and 10 mg/kg i.p.) failed to exert any effects on the severity of dystonia. While the antidystonic efficacy of WIN 55,212-2 (5 mg/kg i.p.) was confirmed, cannabidiol (which has low affinity to cannabinoid receptors) tended to delay the progression of dystonia only at a high dose (150 mg/kg i.p.). The antidystonic and cataleptic effects of WIN 55,212-2 (5 mg/kg i.p.) were completely antagonized by pretreatment with SR 141716A at doses of 2.5 mg/kg (catalepsy) and 10 mg/kg (antidystonic efficacy). These data indicate that the antidystonic efficacy of WIN 55,212-2 is selectively mediated via CB(1) receptors. The lack of prodystonic effects of SR 141716A together with only moderate antidystonic effects of WIN 55,212-2 suggests that reduced activation of cannabinoid CB(1) receptors by endocannabinoids is not critically involved in the dystonic syndrome. In view of previous pathophysiological findings in mutant hamsters, the antidystonic efficacy of WIN 55,212-2 can be explained by modulation of different neurotransmitter systems within the basal ganglia.

Topics: Animals; Benzoxazines; Cannabidiol; Cannabinoid Receptor Modulators; Cannabinoids; Chorea; Cricetinae; Disease Models, Animal; Dystonia; Female; Male; Mesocricetus; Morpholines; Naphthalenes; Piperidines; Pyrazoles; Receptors, Cannabinoid; Receptors, Drug; Rimonabant

Lisuride is a soluble ergolene derivative with endocrine effects similar to but more potent than those of bromocriptine. In nine subjects with idiopathic, postencephalitic, or drug-induced parkinsonism, lisuride at a dosage of 0.05 to 0.15 mg intravenously caused an immediate improvement in tremor, rigidity, akinesia, and postural deformity, but also caused chorea and orofacial dyskinesia. Improvement lasted 2 to 3 hours. Lisuride had little or no effect in a single patient with progressively supranuclear palsy. Oral lisuride therapy, 0.8 to 4.8 mg daily, had similar effects but occasionally caused reduced awareness and hallucinations.

Topics: Administration, Oral; Aged; Benzimidazoles; Chorea; Domperidone; Dose-Response Relationship, Drug; Drug Therapy, Combination; Dyskinesia, Drug-Induced; Ergolines; Female; Growth Hormone; Humans; Injections, Intravenous; Lisuride; Male; Middle Aged; Paralysis; Parkinson Disease; Parkinson Disease, Postencephalitic; Parkinson Disease, Secondary; Piperidines; Prolactin

Topics: Bipolar Disorder; Butyrophenones; Chorea; Drug Therapy; Electromyography; Haloperidol; Humans; Huntington Disease; Mental Disorders; Movement Disorders; Piperidines; Psychotic Disorders; Temperament