Anticholinergic drugs: response of parkinsonism not responsive to levodopa.
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A 41 year old man with parkinsonism and pyramidal signs is described. He was non-responsive to levodopa and dopamine receptor agonists but dramatically responded to trihexyphenidyl. In this patient, brain MRI showed bilateral hyperintensities along the corticospinal tracts on T2 weighted images. PET studies showed a decrease in (18)F-6-fluorodopa uptake in the putamen contralateral to the more affected limbs and normal D(2) receptor binding in the putamen. The PET and MRI findings and responsiveness to antiparkinsonian agents suggested degeneration of nigrostriatal dopaminergic neurons, striatal output pathways, and corticospinal tracts. (+info)
Impaired absorption of chlorpromazine in rats given trihexyphenidyl.
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1 The absorption and tissue distribution of orally administered [14C]-chlorpromazine (CPZ) were compared in trihexyphenidyl (THP; Artane)-treated and control rats. 2 Total radioactivity (CPZ) in the plasma and brain of rats treated with THP was significantly lower whereas total radioactivity in the stomach was significantly higher than in rats not previously treated with THP. 3 Gastric emptying in rats treated with THP was significantly delayed as measured by gastric clearance of a marker [14C]-polyethylene glycol. 4 Transport of [14C]-CPZ in everted sacs was not affected by treatment with THP. 5 Metabolism of [14C]-CPZ by liver homogenates was not affected by treatment with THP. 6 The relationship of delayed gastric emptying in THP-treated rats and their lower plasma and brain levels of [14C]-CPZ after oral administration is discussed. (+info)
Patient with limb girdle dystrophy presenting with dopa-responsive dystonia--a case report.
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Dopa-responsive dystonias are rare. We report a 14-year-old male who was diagnosed as a case of limb girdle dystrophy and had features suggestive of dopa-responsive dystonia. (+info)
Increased anticholinergic challenge-induced memory impairment associated with the APOE-epsilon4 allele in the elderly: a controlled pilot study.
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The degree to which elderly adults experience cognitive impairments from centrally acting anticholinergic drugs is variable, but the cause of this variability is unknown. The present study examined the epsilon4 allele as a possible modulator of the effects of trihexyphenidyl hydrochloride (Artane( trade mark )), an anticholinergic drug, on memory functioning. Of the 24 cognitively intact, elderly participants (age range 62-76), 12 who possessed the epsilon4 allele, participated in a double-blind, randomized, placebo-controlled, crossover, three-way study. All participants were tested after receiving a single oral dose of trihexyphenidyl (1 or 2 mg) or placebo, with a 7-day washout period between sessions. Memory and psychomotor tests were administered at baseline, and at 1, 2.5, and 5 h post-treatment. Results showed that participants with the epsilon4 allele demonstrated significant impairments in delayed recall after both 1 and 2 mg doses of trihexyphenidyl while the non-epsilon4 group did not. Additionally, while acute administration of the 2 mg dose significantly impaired total recall in both epsilon4 and non-epsilon4 carriers, the epsilon4 carriers showed a more persistent impairment. These findings held when participants with the epsilon2 allele were excluded from the analyses. The epsilon4 groups did not differ with respect to psychomotor performance or plasma drug levels. These results provide evidence suggesting that the epsilon4 allele plays a significant role in increasing cognitive sensitivity to trihexyphenidyl and that a temporal component of memory consolidation may be especially vulnerable. A larger study is warranted to confirm these preliminary findings. (+info)
A component analysis of the generation and release of isometric force in Parkinson's disease.
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Paradigms of isometric force control allow study of the generation and release of movement in the absence of complications due to disordered visuomotor coordination. The onset and release of isometric force in Parkinson's disease (PD) was studied, using computerised determinants of latency of response and rate of force generation and release. Components of isometric force control were related to measures of cognitive, affective and clinical motor disability. The effects of treatment were determined by longitudinal study of de novo patients. Patients with PD showed impairment in latency and rate of force change for movement release as well as onset. Rate of force change correlated with depression, clinical motor disability and memory quotient but latency showed no correlation with any of these measures. Treatment improved rate of force release, in concert with clinical motor disability, but not latency. These results suggest dissociations between latency and rate of force change that may be linked to different neurochemical deficits. Further, they demonstrate akinetic deficits in force release that argue against the "neural energy hypothesis" of akinesia. (+info)
Muscarinic preferential M(1) receptor antagonists enhance the discriminative-stimulus effects of cocaine in rats.
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Previous studies of benztropine analogues have found them to inhibit dopamine uptake like cocaine, but with less effectiveness than cocaine in producing behavioral effects related to drug abuse. Studies have assessed whether nonselective muscarinic antagonists decrease the effects of cocaine because many of the benztropine analogues are also muscarinic antagonists. As previous studies were conducted with nonselective muscarinic antagonists and the benztropine analogues show preferential affinity for the M(1) muscarinic receptor subtype, the present study examined interactions of cocaine and the preferential M(1) antagonists, telenzepine (TZP) and trihexyphenidyl (TXP) on subjective effects in rats trained to discriminate cocaine (10 mg/kg, i.p.) from saline injections. Cocaine dose-dependently increased the percentage of responses on the cocaine-appropriate lever, with full substitution at the training dose. In contrast neither TZP nor TXP produced more than 25% cocaine-appropriate responding at any dose. Both M(1) antagonists produced significant leftward shifts in the cocaine dose-effect curve, TZP at 3.0 and TXP at 0.3 and 1.0 mg/kg. The present results indicate that preferential antagonist actions at muscarinic M(1) receptors enhance rather than attenuate the discriminative-stimulus effects of cocaine, and thus those actions unlikely contribute to the reduced cocaine-like effects of BZT analogues. (+info)
Target urinary analytes for the gas chromatographic- mass spectrometric detection of procyclidine and benzhexol in drug abuse cases.
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The two antiparkinsonian drugs procyclidine and benzhexol are presently finding considerable favor for their euphoric hallucinogenic effects among drug abusers in some countries. In anticipation of their possible scheduling in national drug laws, gas chromatography-mass spectrometry (GC-MS) methods for their detection in urine will be required. However, because of uncertainty of the metabolic fate of the two drugs in humans, the urinary target analytes for GC-MS detection were not well defined. The problem was addressed in the present study in which it was found that mono-hydroxy metabolites, where hydroxylation took place at the cyclohexane ring in both drugs, could be endorsed as the major target analytes. The metabolites could only be detected as the mono- and/or di-trimethylsilyl (TMS) derivatives. The predominance of either derivative depended on the temperature and time of heating with the derivatizing reagent. Because of the basic properties of the hydroxy metabolites, analytic method optimization was needed for their detection in urine included extraction under basic pH conditions. Urine hydrolysis with beta-glucuronidase did not have an effect on the recovery of the metabolites, but was usually performed in search for other drugs. Because of the relative abundance of ions, the electron impact mass spectra of the mono-TMS derivatives and the chemical ionization (CI) mass spectra of the mono- and di-TMS derivatives of the hydroxy metabolites of both drugs were found to be more structurally informative. The CI mass spectra of the di- TMS derivatives have the additive advantage of being potentially useful for quantitative analysis. (+info)
Anticholinergics boost the pathological process of neurodegeneration with increased inflammation in a tauopathy mouse model.
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