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Jack J Chen

Publications and source records attributed to Jack J Chen.

13 recordsLinked to original sources
PubMed2006

Synthesis and evaluation of novel 8,5-fused bicyclic peptidomimetic compounds as interleukin-1beta converting enzyme (ICE) inhibitors.

An 8,5-fused bicyclic peptidomimetic ring system generated by a stereoselective ring metathesis reaction was elaborated into potent inhibitors of interleukin-1beta converting enzyme (ICE, caspase-1). Multiple compounds were found that exhibited ICE IC50 values < 10 nM and were selective over caspase-3 and caspase-8. These active analogs generally possessed good activity (IC50 values < 100 nM) in a whole cell assay measuring IL-1beta production. Pharmacokinetic analysis of the ethyl acetal prodrug form of a selected active lead revealed a compound with a reasonable plasma half-life (1.1 h) and good oral bioavailability (30%).

Animals↗
PubMed2006

Duplicate publication.

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Duplicate Publications as Topic↗
PubMed2006

Rasagiline: A second-generation monoamine oxidase type-B inhibitor for the treatment of Parkinson's disease.

PURPOSE: The pharmacology, pharmacokinetics, clinical efficacy, and safety of rasagiline are reviewed. SUMMARY: Rasagiline is a novel, investigational propargylamine that irreversibly and selectively inhibits monoamine oxidase type B (MAO-B). Rasagiline demonstrates complete and selective inhibition of MAO-B and is at least five times more potent than selegiline. Unlike selegiline, which is metabolized to amphetamine derivatives, rasagiline is biotransformed to the nonamphetamine compound aminoindan. Clinical studies have revealed that rasagiline is associated with improved outcomes in patients with early Parkinson's disease (PD) and also reduces "off" time in patients with moderate to advanced PD with motor fluctuations. Rasagiline is rapidly absorbed by the gastrointestinal tract and readily crosses the blood-brain barrier. The optimal therapeutic dosage is 0.5-1 mg administered orally once daily. Rasagiline appears to be well tolerated, although elderly patients may be more prone to treatment-emergent adverse cardiovascular and psychiatric effects. At the recommended therapeutic dosage of up to 1 mg once daily, tyramine restriction is unnecessary. In addition to MAO-B inhibition, rasagiline has demonstrated neuroprotective properties in experimental laboratory models. The mechanisms whereby rasagiline exerts neuroprotective effects are multifactorial and include upregulation of cellular antioxidant activity and antiapoptotic factors. CONCLUSION: Rasagiline is an investigational selective and irreversible inhibitor of MAO-B that has demonstrated efficacy and safety for the treatment of PD. Whether rasagiline is associated with clinically significant neuroprotection is the subject of ongoing clinical trials.

Clinical Trials as Topic↗
PubMed2006

Update on apomorphine for the rapid treatment of hypomobility ("off") episodes in Parkinson's disease.

As Parkinson's disease progresses, fluctuations between akinesia, or hypomobility ("off" times), and mobility ("on" times) increase in frequency despite optimized pharmacotherapy. Motor fluctuations include predictable shortening of therapeutic effects, nocturnal or early morning akinesia, random hypomobility, and delayed mobility (variable responses to individual doses of drugs). Current oral antiparkinson drugs are inadequate for rapid and consistent relief of symptoms during hypomobility. Apomorphine, an injectable dopamine agonist recently introduced in the United States, is indicated for the management of hypomobility associated with advanced Parkinson's disease. Subcutaneous apomorphine is effective for rapid and consistent rescue from hypomobility, with a magnitude of motor improvement similar to that of levodopa. The effect begins within 20 minutes after dosing and lasts approximately 100 minutes. Therapeutic rescue doses are 2-6 mg, and patients typically require approximately three rescue doses/day. Apomorphine is associated with a clinically significant potential to cause nausea and orthostatic hypotension. These potential effects can be managed with antiemetic prophylaxis and appropriate determination of the therapeutic rescue dose.

Antiparkinson Agents↗
PubMed2006

Nonparkinsonism movement disorders in the elderly.

OBJECTIVE: The primary objective of this article is to review the clinical presentation and pharmacologic management of essential tremor and tardive dyskinesia. DATA SOURCES: The MEDLINE (1966-August 2005), Cochrane Database of Systematic Reviews, and International Pharmaceutical Abstracts (1970-August 2005) databases were searched for original research and review articles published in English. The search terms were essential tremor and tardive dyskinesia. Reference lists from articles were also consulted. DATA SYNTHESIS: Essential tremor is most commonly manifested as a postural or action tremor of the upper extremities. Midline regions such as the head and voice are also commonly affected. Based on review of the literature, propranolol and primidone are the current pharmacologic mainstays for treating essential tremor of the upper extremities. The choice of agent depends on patient-specific factors such as underlying medical conditions. Other agents with demonstrated efficacy include gabapentin and topiramate. Benzodiazepines are effective adjunctive agents, but should be utilized judiciously in the elderly. Botulinum toxin is effective for essential tremor of the voice and head. Surgery is very effective, but may not be appropriate in the frail elderly and should be avoided in the presence of cognitive impairment. Tardive dyskinesia is characterized by involuntary choreoathetoid movements of the orofacial region. For the management of tardive dyskinesia, emphasis is placed on primary prevention and early recognition of signs and symptoms. In some cases, discontinuation of the offending agent can result in reversal of symptoms. If a conventional neuroleptic is the causative agent, switching to an atypical antipsychotic may be helpful. Overall, few treatments have proven to be consistently useful. Other agents that may be helpful include acetylcholinesterase inhibitors, amantadine, baclofen, benzodiazepines, branched chain amino acids, gabapentin, levetiracetam, pyridoxine, verapamil, and vitamin E. CONCLUSION: Current pharmacologic agents for essential tremor can be expected to provide partial benefit. However, agents for the symptomatic management of tardive dyskinesia are limited, and additional research is warranted in this area.

Adrenergic Uptake Inhibitors↗
PubMed2005

A review of intermittent subcutaneous apomorphine injections for the rescue management of motor fluctuations associated with advanced Parkinson's disease.

BACKGROUND: As Parkinson's disease (PD) progresses,despite optimized pharmacotherapy, patients experience more frequent fluctuations between symptomatic improvement ("on" times) and the return of motor features ("off" times). Apomorphine, the first injectable dopamine agonist available in the United States, is indicated for the acute treatment of "off" episodes (eg, end-of-dose wearing-off episodes, unpredictable "on/off" episodes) in patients with advanced PD who are receiving medically optimal antiparkinsonian therapy. OBJECTIVE: This article reviews the pharmacology,clinical efficacy, and tolerability of intermittent subcutaneous apomorphine injections for the management of "off" episodes in patients with PD. METHODS: MEDLINE (1966-July 2005), the Cochrane Database of Systematic Reviews, and International Pharmaceutical Abstracts (1970-July 2005) were searched for original research and review articles published in English. The search terms were apomorphine and Parkinson's disease. The reference lists of articles were also consulted, as was selected information provided by the manufacturer of apomorphine. All relevant identified studies on intermittent subcutaneous administration of apomorphine were included in the review; trials of continuous subcutaneous infusion and non-subcutaneous administration of apomorphine were excluded. RESULTS: Intermittent subcutaneous administration of apomorphine produced consistent rescue from "of" episodes in patients with advanced PD, with a symptomatic motor improvement between the predose "off" state and postdose "on" state similar to that achieved with levodopa. The onset of effect occurred within 20 minutes, and the duration of effect was approximately 100 minutes. The therapeutic rescue dose ranged from 2 to 6 mg. During the clinical development program for subcutaneously injected apomorphine, patients required a mean of approximately 3 rescue doses per day. Common adverse effects occurring in > or =20% of patients were injection-site reaction, yawning, dyskinesias, drowsiness, nausea and vomiting, dizziness or postural dizziness, and rhinorrhea. CONCLUSIONS: The available clinical studies indicate that apomorphine is effective in providing prompt and consistent rescue from "off" episodes in patients with PD. Antiemetic prophylaxis and close medical supervision are recommended when initiating apomorphine therapy.

Antiparkinson Agents↗
PubMed2005

Clinical pharmacology of rasagiline: a novel, second-generation propargylamine for the treatment of Parkinson disease.

Rasagiline is a novel second-generation propargylamine that irreversibly and selectively inhibits monoamine oxidase type B (MAO-B). For the management of Parkinson disease (PD), rasagiline is efficacious across the span of PD stages ranging from monotherapy in early disease to adjunctive treatment in patients with advancing disease and motor fluctuations. Rasagiline completely and selectively inhibits MAO-B with a potency 5 to 10 times greater than selegiline. Unlike the prototype propargylamine selegiline, which is metabolized to amphetamine derivatives, rasagiline is biotransformed to aminoindan, a non-amphetamine compound. Rasagiline is well tolerated with infrequent cardiovascular or psychiatric side effects, and at the recommended therapeutic dose of up to 1 mg once daily, tyramine restriction is unnecessary. In addition to MAO-B inhibition, the propargylamine chain also confers dose-related antioxidant and antiapoptotic effects, which have been associated with neuroprotection in multiple experimental models. Thus, in addition to symptomatic benefits, rasagiline offers the promise of clinically relevant neuroprotection.

Animals↗
PubMed2003

The white coat.

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Career Choice↗
PubMed2003

Essential tremor: diagnosis and treatment.

Essential tremor is a common movement disorder in adults that interferes with the performance of functional and social activities. Differentiation of essential tremor from other tremor syndromes is important in order to provide appropriate patient education and therapy. The mainstays of pharmacotherapy are propranolol and primidone; however, in selected patients, agents such as alcohol, benzodiazepines, botulinum toxin, and gabapentin may provide symptomatic benefits. Advances in surgical interventions, such as stereotactic thalamotomy and thalamic deep brain stimulation, offer patients an alternative treatment modality when pharmacotherapy is inadequate. A treatment algorithm is provided to guide clinicians in the management of patients with essential tremor.

Acetates↗
PubMedDate not supplied

Solid-supported synthesis of putative peptide beta-turn mimetics via Ugi reaction for diketopiperazine formation.

The scope and limitations of the solid-supported synthesis of a bicyclic diketopiperazine, an internal, putative peptide beta-turn mimetic, are presented. The 4CC multicomponent Ugi reaction of alpha-N-Boc-diaminopropionic acid resin ester (an amine input), optically active alpha-bromoacid, aldehyde, and isocyanide is the key step in the proposed synthetic protocol. Application of cyclitive cleavage as the final step led to desired products in high purity.

Biomimetic Materials↗