- Disabling tremor induced by long-term use of sodium valproate and lamotrigine: Case report. [Case Reports]
- MMedicine (Baltimore) 2017; 96(47):e8711
- CONCLUSIONS: Considering the wide and long-term utilization of VPA and LTG, healthcare providers should be aware of them as a possible cause of tremor. When necessary, an attempt of discontinuing the suspected drugs should be made to confirm the diagnosis, instead of symptomatic treatment, especially when the adverse event was severe and fatal.
- Persistent oromandibular dystonia and angioedema secondary to haloperidol. [Journal Article]
- BCBMJ Case Rep 2017 Oct 04; 2017
- We report a case in a young man who developed acute, persistent and painful tongue protrusion followed by swelling for more than 24 hours. He had relapse symptoms of schizophrenia and had recently re...
We report a case in a young man who developed acute, persistent and painful tongue protrusion followed by swelling for more than 24 hours. He had relapse symptoms of schizophrenia and had recently received a single dose of parenteral haloperidol to manage his agitation. His record showed history of similar event and he has been taking atypical antipsychotic for maintenance. Mental state examination on admission revealed an agitated man with disorganised speech, restricted affect, auditory hallucination and persecutory delusion. His dystonia and oedema improved after 3 days. His mental status also recovered with the maintenance of low-potency antipsychotic and anticholinergic antiparkinsonian medications.
- Altered detrusor contractility in MPTP-treated common marmosets with bladder hyperreflexia. [Journal Article]
- PlosPLoS One 2017; 12(5):e0175797
- Bladder hyperreflexia is a common non-motor feature of Parkinson's disease. We now report on the contractility of the isolated primate detrusor strips devoid of nerve input and show that following MP...
Bladder hyperreflexia is a common non-motor feature of Parkinson's disease. We now report on the contractility of the isolated primate detrusor strips devoid of nerve input and show that following MPTP, the amplitude and frequency of spontaneous contraction was increased. These responses were unaffected by dopamine D1 and D2 receptor agonists A77636 and ropinirole respectively. Contractions by exogenous carbachol, histamine or ATP were similar and no differences in the magnitude of noradrenaline-induced relaxation were seen in detrusor strip obtained from normal and MPTP-treated common marmosets (Callithrix jacchus). However, the neurogenic contractions following electrical field stimulation of the intrinsic nerves (EFS) were markedly greater in strips obtained from MPTP treated animals. EFS evoked non-cholinergic contractions following atropine were also greater but the contribution of the cholinergic innervation as a proportion of the overall contraction was smaller in the detrusor strips of MPTP treated animals, suggesting a preferential enhancement of the non-cholinergic transmission. Although dopaminergic mechanism has been proposed to underlie bladder hyperreflexia in MPTP-treated animals with intact bladder, the present data indicates that the increased neurogenically mediated contractions where no extrinsic innervation exists might be due to long-term adaptive changes locally as a result of the loss of the nigrostriatal output.
- σ Receptor Effects of N-Substituted Benztropine Analogs: Implications for Antagonism of Cocaine Self-Administration. [Journal Article]
- JPJ Pharmacol Exp Ther 2017; 362(1):2-13
- Several N-substituted benztropine (BZT) analogs are atypical dopamine transport inhibitors as they have affinity for the dopamine transporter (DAT) but have minimal cocaine-like pharmacologic effects...
Several N-substituted benztropine (BZT) analogs are atypical dopamine transport inhibitors as they have affinity for the dopamine transporter (DAT) but have minimal cocaine-like pharmacologic effects and can block numerous effects of cocaine, including its self-administration. Among these compounds, N-methyl (AHN1-055), N-allyl (AHN2-005), and N-butyl (JHW007) analogs of 3α-[bis(4'-fluorophenyl)methoxy]-tropane were more potent in antagonizing self-administration of cocaine and d-methamphetamine than in decreasing food-maintained responding. The antagonism of cocaine self-administration (0.03-1.0 mg/kg per injection) with the above BZT analogs was reproduced in the present study. Further, the stimulant-antagonist effects resembled previously reported effects of pretreatments with combinations of standard DAT inhibitors and σ1-receptor (σ1R) antagonists. Therefore, the present study examined binding of the BZT analogs to σRs, as well as their in vivo σR antagonist effects. Each of the BZT analogs displaced radiolabeled σR ligands with nanomolar affinity. Further, self-administration of the σR agonist DTG (0.1-3.2 mg/kg/injection) was dose dependently blocked by AHN2-005 and JHW007 but potentiated by AHN1-055. In contrast, none of the BZT analogs that were active against DTG self-administration was active against the self-administration of agonists at dopamine D1-like [R(+)-SKF 81297, (±)-SKF 82958 (0.00032-0.01 mg/kg per injection each)], D2-like [R(-)-NPA (0.0001-0.0032 mg/kg per injection), (-)-quinpirole (0.0032-0.1 mg/kg per injection)], or μ-opioid (remifentanil, 0.0001-0.0032 mg/kg per injection) receptors. The present results indicate that behavioral antagonist effects of the N-substituted BZT analogs are specific for abused drugs acting at the DAT and further suggest that σR antagonism contributes to those actions.
- The Isomeric Preference of an Atypical Dopamine Transporter Inhibitor Contributes to Its Selection of the Transporter Conformation. [Journal Article]
- ACACS Chem Neurosci 2017 Aug 16; 8(8):1735-1746
- Cocaine, a widely abused psychostimulant, inhibits the dopamine transporter (DAT) by trapping the protein in an outward-open conformation, whereas atypical DAT inhibitors such as benztropine have low...
Cocaine, a widely abused psychostimulant, inhibits the dopamine transporter (DAT) by trapping the protein in an outward-open conformation, whereas atypical DAT inhibitors such as benztropine have low abuse liability and prefer less outward-open conformations. Here, we use a spectrum of computational modeling and simulation approaches to obtain the underlying molecular mechanism in atomistic detail. Interestingly, our quantum mechanical calculations and molecular dynamics (MD) simulations suggest that a benztropine derivative JHW007 prefers a different stereoisomeric conformation of tropane in binding to DAT compared to that of a cocaine derivative, CFT. To further investigate the different inhibition mechanisms of DAT, we carried out MD simulations in combination with Markov state modeling analysis of wild-type and Y156F DAT in the absence of any ligand or the presence of CFT or JHW007. Our results indicate that the Y156F mutation and CFT shift the conformational equilibrium toward an outward-open conformation, whereas JHW007 prefers an inward-occluded conformation. Our findings reveal the mechanistic details of DAT inhibition by JHW007 at the atomistic level, which provide clues for rational design of atypical inhibitors.
- Simultaneous usage of dementia medications and anticholinergics among Asians and Pacific Islanders. [Journal Article]
- PPsychogeriatrics 2017; 17(6):423-429
- CONCLUSIONS: Simultaneous prescribing of cholinesterase inhibitors, memantine, and anticholinergic medications was significantly less common than in previous studies, with some ethnic variability. The less frequent occurrence of concurrent medications in the Asian population may be because of variations in the rate of indications or in tolerability for anticholinergic medications among the population.
- [A differential approach to the improvement of prevention and correction of neuroleptic side extrapyramidal disorders with pantogam activ in patients with schizophrenia]. [Journal Article]
- ZNZh Nevrol Psikhiatr Im S S Korsakova 2017; 117(2):72-80
- CONCLUSIONS: PA in the combination with THP has demonstrated the clear neuroprotective effect on the development, frequency and clinical presentations of neurological side-effects. The РА can be recommended as a drug of choice for correction and prevention of neuroleptic side-effects, it promotes their tolerability and improves quality of life during the course treatment.
- The antidepressant-like effects of biperiden may involve BDNF/TrkB signaling-mediated BICC1 expression in the hippocampus and prefrontal cortex of mice. [Journal Article]
- PBPharmacol Biochem Behav 2017; 157:47-57
- Preclinical and clinical studies suggest that neuronal muscarinic acetylcholine receptor (M-AchR) antagonists have antidepressant-like properties. Despite the recent interest in bicaudal C homolog 1 ...
Preclinical and clinical studies suggest that neuronal muscarinic acetylcholine receptor (M-AchR) antagonists have antidepressant-like properties. Despite the recent interest in bicaudal C homolog 1 gene (BICC1) as a target for the treatment of depression, the upstream signaling molecules that regulate BICC1 are unknown, and very few studies have addressed the involvement of BICC1 in the antidepressant-like effects of the selective M1-AchR inhibitor, biperiden. Growing evidence indicates that activation of brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase receptor B (TrkB) signaling may be involved in antidepressant-like activities. In this study, we investigated the role of BDNF/TrkB signaling in the regulation of BICC1 expression in the chronic unpredictable stress (CUS) mouse model of depression. Furthermore, we also examined whether BDNF/TrkB signaling contributes to the antidepressant-like effects of biperiden via down-regulation of BICC1 in the hippocampus and prefrontal cortex of mice. Our current data show that CUS exposure induced significant depression-like behaviors, down-regulation of BDNF/TrkB signaling and up-regulation of BICC1 in the hippocampus and prefrontal cortex of mice. However, biperiden significantly alleviated the CUS-induced abnormalities. Moreover, we found that the effects of biperiden were antagonized by pretreatment with the TrkB antagonist K252a. Our results indicate that BDNF/TrkB signaling may be the major upstream mediator of BICC1 involvement in the antidepressant-like effects of biperiden.
- Association between cognitive impairment and urinary dysfunction in Parkinson's disease. [Journal Article]
- JNJ Neural Transm (Vienna) 2017; 124(5):543-550
- Urinary dysfunction (UD) is a common non-motor feature of Parkinson's disease (PD), and might be secondary to neurodegeneration involving cortical and subcortical brain areas. The possible link betwe...
Urinary dysfunction (UD) is a common non-motor feature of Parkinson's disease (PD), and might be secondary to neurodegeneration involving cortical and subcortical brain areas. The possible link between UD and cognitive deficits has never been examined in frontal cortex impairment, and is still not completely understood in PD. In the present study, 94 PD patients underwent a comprehensive motor, cognitive and non-motor assessment. It was shown that 55.3% of patients reported UD, of which 17% needed specific urological treatment. Patients who reported UD performed worse on global cognition (PANDA, p = .05), visuo-constructive functions (CERAD/praxis, p = .03; and Figure Test, p = .03), and instrumental activities of daily living functions (IADL, p = .03), than patients without UD. The group with UD medication performed worse on global cognition (PANDA, p = .02) and visuo-constructive functions (CERAD/praxis, p = .05; CERAD/praxis recall, p = .05) than the UD group without medication, independent of anticholinergic treatment effect. Our findings suggest an association between cognitive impairment and UD in PD independent from symptomatic treatment.
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- Effects of biperiden and acute tryptophan depletion and their combination on verbal word memory and EEG. [Randomized Controlled Trial]
- PPsychopharmacology (Berl) 2017; 234(7):1135-1143
- CONCLUSIONS: These results indicate that both BIP and ATD impair episodic memory. However, an interaction between the serotonergic and cholinergic system on memory performance is not supported.