Dopaminergic versus anticholinergic treatment effects on physiologic complexity of hand tremor in Parkinson's disease: A randomized crossover study.

AIMS: Parkinsonian tremor (PT) is regulated by numerous neurophysiological components across multiple temporospatial scales. The dynamics of tremor fluctuation are thus highly complex. This study aimed to explore the effects of different medications on tremor complexity, and how the underlying factors contribute to such tremor complexity. METHODS: In this study, 66 participants received a 2-mg dose of benzhexol or a pre-determined dose of levodopa at two study visits in a randomized order. Before and after taking the medications, tremor fluctuation was recorded using surface electromyography electrodes and accelerometers in resting, posture, and weighting conditions with and without a concurrent cognitive task. Tremor complexity was quantified using multiscale entropy. RESULTS: Tremor complexity in resting (p = 0.002) and postural condition (p < 0.0001) was lower when participants were performing a cognitive task compared to a task-free condition. After taking levodopa and benzhexol, participants had increased (p = 0.02-0.03) and decreased (p = 0.03) tremor complexity compared to pre-medication state, respectively. Tremor complexity and its changes as induced by medications were significantly correlated with clinical ratings and their changes (ß = -0.23 to -0.39; p = 0.002-0.04), respectively. CONCLUSION: Tremor complexity may be a promising marker to capture the pathophysiology underlying the development of PT, aiding the characterization of the effects medications have on PT regulation.

Pharmacological interventions for antipsychotic-related sialorrhea: a systematic review and network meta-analysis of randomized trials.

Antipsychotic-induced sialorrhea carries a significant burden, but evidence-based treatment guidance is incomplete, warranting network meta-analysis (NMA) of pharmacological interventions for antipsychotic-related sialorrhea. PubMed Central/PsycInfo/Cochrane Central database/Clinicaltrials.gov/WHO-ICTRP and the Chinese Electronic Journal Database (Qikan.cqvip.com) were searched for published/unpublished RCTs of antipsychotic-induced sialorrhea (any definition) in adults, up to 06/12/2023. We assessed global/local inconsistencies, publication bias, risk of bias (RoB2), and confidence in the evidence, conducting subgroup/sensitivity analyses. Co-primary efficacy outcomes were changes in saliva production (standardized mean difference/SMD) and study-defined response (risk ratios/RRs). The acceptability outcome was all-cause discontinuation (RR). Primary nodes were molecules; the mechanism of action (MoA) was secondary. Thirty-four RCTs entered a systematic review, 33 NMA (n = 1958). All interventions were for clozapine-induced sialorrhea in subjects with mental disorders. Regarding individual agents and response, metoclopramide (RR = 3.11, 95% C.I. = 1.39-6.98), cyproheptadine, (RR = 2.76, 95% C.I. = 2.00-3.82), sulpiride (RR = 2.49, 95% C.I. = 1.65-3.77), propantheline (RR = 2.39, 95% C.I. = 1.97-2.90), diphenhydramine (RR = 2.32, 95% C.I. = 1.88-2.86), benzhexol (RR = 2.32, 95% C.I. = 1.59-3.38), doxepin (RR = 2.30, 95% C.I. = 1.85-2.88), amisulpride (RR = 2.23, 95% C.I. = 1.30-3.81), chlorpheniramine (RR = 2.20, 95% C.I. = 1.67-2.89), amitriptyline (RR = 2.09, 95% C.I. = 1.34-3.26), atropine, (RR = 2.03, 95% C.I. = 1.22-3.38), and astemizole, (RR = 1.70, 95% C.I. = 1.28-2.26) outperformed placebo, but not glycopyrrolate or ipratropium. Across secondary nodes (k = 28, n = 1821), antimuscarinics (RR = 2.26, 95% C.I. = 1.91-2.68), benzamides (RR = 2.23, 95% C.I. = 1.75-3.10), TCAs (RR = 2.23, 95% C.I. = 1.83-2.72), and antihistamines (RR = 2.18, 95% C.I. = 1.83-2.59) outperformed placebo. In head-to-head comparisons, astemizole and ipratropium were outperformed by several interventions. All secondary nodes, except benzamides, outperformed the placebo on the continuous efficacy outcome. For nocturnal sialorrhea, neither benzamides nor atropine outperformed the placebo. Active interventions did not differ significantly from placebo regarding constipation or sleepiness/drowsiness. Low-confidence findings prompt caution in the interpretation of the results. Considering primary nodes' co-primary efficacy outcomes and head-to-head comparisons, efficacy for sialorrhea is most consistent for the following agents, decreasing from metoclopramide through cyproheptadine, sulpiride, propantheline, diphenhydramine, benzhexol, doxepin, amisulpride, chlorpheniramine, to amitriptyline, and atropine (the latter not for nocturnal sialorrhea). Shared decision-making with the patient should guide treatment decisions regarding clozapine-related sialorrhea.

(R,S)-trihexyphenidyl, acting via a muscarinic receptor-independent mechanism, inhibits hippocampal glutamatergic and GABAergic synaptic transmissions: Potential relevance for treatment of organophosphorus intoxication.

Preclinical studies have reported that, compared to the muscarinic receptor (mAChR) antagonist atropine, (R,S)-trihexyphenidyl (THP) more effectively counters the cholinergic crisis, seizures, and neuropathology triggered by organophosphorus (OP)-induced acetylcholinesterase (AChE) inhibition. The greater effectiveness of THP was attributed to its ability to block mAChRs and N-methyl-d-aspartate-type glutamatergic receptors (NMDARs) in the brain. However, THP also inhibits α7 nicotinic receptors (nAChRs). The present study examined whether THP-induced inhibition of mAChRs, α7 nAChRs, and NMDARs is required to suppress glutamatergic synaptic transmission, whose overstimulation sustains OP-induced seizures. In primary hippocampal cultures, THP (1-30 µM) suppressed the frequency of excitatory and inhibitory postsynaptic currents (EPSCs and IPSCs, respectively) recorded from neurons in nominally Mg2+-free solution. A single sigmoidal function adequately fit the overlapping concentration-response relationships for THP-induced suppression of IPSC and EPSC frequencies yielding an IC50 of 6.3 ± 1.3 µM. Atropine (1 µM), the NMDAR antagonist d,l-2-amino-5-phosphonopentanoic acid (D,L-AP5, 50 µM), and the α7 nAChR antagonist methyllycaconitine (MLA, 10 nM) did not prevent THP-induced inhibition of synaptic transmission. THP (10 µM) did not affect the probability of transmitter release because it had no effect on the frequency of miniature IPSCs and EPSCs recorded in the presence of tetrodotoxin. Additionally, THP had no effect on the amplitudes and decay-time constants of miniature IPSCs and EPSCs; therefore, it did not affect the activity of postsynaptic GABAA and glutamate receptors. This study provides the first demonstration that THP can suppress action potential-dependent synaptic transmission via a mechanism independent of NMDAR, mAChR, and α7 nAChR inhibition.

[Changes in Test Methods for Internationalization in the Japanese Pharmacopoeia (Part 3): Establishment of a Quantitative Method for Sodium Cromoglicate and Trihexyphenidyl Hydrochloride Using HPLC Analysis].

The Japanese Pharmacopoeia (JP) is an official normative publication for establishing the authenticity and properties and maintaining the quality of pharmaceutical products in Japan. The JP is revised every five years and partially revised in order to respond to the progress of science and technology, the demand for medical care, and international harmonization. Thus, "Internationalization of the JP" is one of the most important issues to address for the revision of the JP, which is also referred to the basic principles for the preparation of the JP 19th edition. For instance, the incorporation of the test methods that have been used in other pharmacopeias, such as the European Pharmacopoeia (EP) and the United States Pharmacopeia (USP), into the JP is one of promising approaches. From this perspective, we have recently reported changes in test methods, establishment of a quantitative test method for the JP-listed clonidine hydrochloride as well as lorazepam from using a potentiometric titration method to using HPLC method. As our ongoing study to change test methods for internationalization, we selected sodium cromoglicate and trihexyphenidyl hydrochloride. Each pharmaceutical product is analyzed using a potentiometric titration method as listed in the 18th JP; however, both the EP and the USP use HPLC method for quantitative analysis of these drugs. In this study, we synthesized the related impurities of sodium cromoglicate and trihexyphenidyl hydrochloride listed in the EP and determined their purities using quantitative NMR. The separation conditions of these compounds were examined using HPLC and simultaneous analyses were performed.

Trihexyphenidyl in young children with dystonic cerebral palsy: A single arm study.

PURPOSE: The incidence of dystonic cerebral palsy causing significant morbidity is on the rise. There is a paucity of evidence for the management of dystonia in children. METHODS: Forty-one children aged 6 months-5 years with predominantly dystonic cerebral palsy were started on a predetermined protocol of trihexyphenidyl (0.25-0.52 mg/kg) and followed up at 3, 6 and 12 weeks. Dystonia severity, motor function and developmental age at baseline and 12 weeks were compared using the Global Dystonia Scale (GDS), the Gross Motor Function Measure (GMFM), and Fine Motor/Perceptual Subscale of the Early Developmental Profile-2. Thirty-four children completed the entire 12 weeks of intervention. RESULTS: The mean age of participants was 25±11 months. A significant decrease in median total dystonia scores on the GDS was observed post-intervention (74.5 to 59, p < 0.0001), and 64% of participants gained motor milestones. GMFM scores increased significantly from a median of 19.8% pre-intervention to 26.5% post-intervention (p < 0.0001). There was improvement in the fine motor domain as compared to the baseline (p < 0.0001). The number of children classified at Gross Motor Function Classification System levels 1 and 2 increased to 47.05% from 5.88% in the pre-intervention group. CONCLUSION: Trihexyphenidyl significantly improved dystonia, motor function and development in children with dystonic cerebral palsy in this study. Additional studies are needed to clarify its role in larger numbers of children with this condition.

Gabapentin as Add-on Therapy to Trihexyphenidyl in Children with Dyskinetic Cerebral Palsy: A Randomized, Controlled Trial.

OBJECTIVE: To compare the efficacy of gabapentin as add-on therapy to trihexyphenidyl in the treatment of children with dyskinetic cerebral palsy (CP). METHODS: An open-labelled, randomized, controlled trial was conducted among children aged 3-9 y with dyskinetic CP [Gross Motor Functional Classification System (GMFCS) 4-5]. Participants were assigned into two groups: gabapentin with trihexyphenidyl (n = 30) and trihexyphenidyl alone (n = 30). Dyskinesia Impairment Scale (DIS), Dystonia Severity Assessment Plan (DSAP), and International Classification of Functioning, Disability, and Health-Children and Youth Version (ICF-CY) were measured at baseline, 4 and 12 wk. RESULTS: There was significant reduction in baseline dystonia in both the groups (DIS: p < 0.001; DSAP: p = 0.007; ICF-CY: p < 0.001) but when data were compared between the groups, there was no significant difference in the severity of dystonia at 4 wk and at 12 wk (DIS: p = 0.09; DSAP: p = 0.49; ICF-CY: p = 0.25). Constipation was the commonest side effect observed in both the groups [3 (11.5%) vs. 4 (14.3%)]. CONCLUSION: Trihexyphenidyl alone is as effective as combination of gabapentin with trihexyphenidyl in decreasing the severity of dystonia at 12 wk. Hence, there is no added benefit of gabapentin as add-on therapy for dystonia among children with dyskinetic CP. TRIAL REGISTRATION: CTRI/2019/04/018603.

Effects of trihexyphenidyl on prefrontal executive function and spontaneous neural activity in patients with tremor-dominant Parkinson's disease: An fNIRS study.

INTRODUCTION: The use of the anti-parkinsonian drug trihexyphenidyl (THP) to treat patients with Parkinson's disease (PD), particularly those with tremor-dominant PD (tdPD), has been well documented. Despite growing concerns about THP causing cognitive decline in tdPD patients, the underlying neural correlates remain unclear. Therefore, we investigated the effects of THP on prefrontal executive function and spontaneous neural activity in patients with tdPD by utilizing functional near-infrared spectroscopy (fNIRS). METHODS: We recruited 30 patients with tdPD, including 15 patients receiving THP and 15 patients not receiving THP. We performed comprehensive neuropsychological and clinical assessments to evaluate each patient's cognitive function, mental status, and clinical symptoms. We measured brain activation elicited from the verbal fluency task (VFT) and changes in amplitude of low-frequency fluctuations (ALFF) at rest to investigate executive function and spontaneous neural activity, respectively. In addition, we examined the relationship between altered activation during task and resting state and neuropsychological and clinical data. RESULTS: Compared with tdPD patients not taking THP, tdPD patients taking THP showed no differences on neuropsychological tests. However, there was insufficient activity of the dorsolateral prefrontal cortex (DLPFC) during VFT and reduced ALFF values for the DLPFC, ventrolateral prefrontal cortex (VLPFC), and the orbitofrontal cortex (OFC) related to the frontoparietal network (FPN) at rest. Furthermore, ALFF values of the VLPFC were positively correlated with scores of multiple cognitive domain functions. CONCLUSION: These findings suggest that THP treatment may lead to prefrontal dysfunction in tdPD patients, attenuating brain activation in executive function and cognition-related spontaneous neural activity.

Trihexyphenidyl increases delta activity in non-rapid eye movement sleep without impairing cognitive function in rodent models.

Both human and rodent studies suggest the link between non-rapid eye movement (NREM) sleep and cognition. Recent study indicated that selective activation of cholinergic neurons in basal forebrain inhibits electroencephalogram (EEG) delta power and shortens NREM sleep. In the current study, we aimed to test the pharmacological effect of trihexyphenidyl (THP), a selective muscarinic M1 receptor antagonist, on EEG power spectra and sleep with or without the selective activation of basal forebrain cholinergic neurons. THP (1, 2, and 3 mg/kg) was administrated intraperitoneally in natural sleep phase. Basal forebrain cholinergic neurons expressing modified G protein-coupled muscarinic receptors (hM3Dq) were activated by intraperitoneal injection of clozapine-N-oxide in ChAT-IRES-Cre mice. EEG and electromyogram (EMG) signals were recorded in freely moving mice to analyze EEG power spectrum and sleep hypnogram. Y-maze and novel object recognition tests were used for testing cognition. THP 1 mg/kg significantly increased EEG delta power and facilitated NREM sleep in wildtype mice, while THP 3 mg/kg was required in ChAT-IRES-Cre mice treated with clozapine-N-oxide. THP with dosage up to 8 mg/kg did not induce cognitive impairments in wildtype mice. EEG delta power of NREM sleep is often used as an indicator of sleep depth or sleep quality, which tightly link with sleep-dependent cognition. Taken together, the data collected from rodents hinted that, THP could possibly be used as the NREM sleep facilitator in humans.

Blockade of M4 muscarinic receptors on striatal cholinergic interneurons normalizes striatal dopamine release in a mouse model of TOR1A dystonia.

Trihexyphenidyl (THP), a non-selective muscarinic receptor (mAChR) antagonist, is commonly used for the treatment of dystonia associated with TOR1A, otherwise known as DYT1 dystonia. A better understanding of the mechanism of action of THP is a critical step in the development of better therapeutics with fewer side effects. We previously found that THP normalizes the deficit in striatal dopamine (DA) release in a mouse model of TOR1A dystonia (Tor1a+/ΔE knockin (KI) mice), revealing a plausible mechanism of action for this compound, considering that abnormal DA neurotransmission is consistently associated with many forms of dystonia. However, the mAChR subtype(s) that mediate the rescue of striatal dopamine release remain unclear. In this study we used a combination of pharmacological challenges and cell-type specific mAChR conditional knockout mice of either sex to determine which mAChR subtypes mediate the DA release-enhancing effects of THP. We determined that THP acts in part at M4 mAChR on striatal cholinergic interneurons to enhance DA release in both Tor1a+/+ and Tor1a+/ΔE KI mice. Further, we found that the subtype selective M4 antagonist VU6021625 recapitulates the effects of THP. These data implicate a principal role for M4 mAChR located on striatal cholinergic interneurons in the mechanism of action of THP and suggest that subtype selective M4 mAChR antagonists may be effective therapeutics with fewer side effects than THP for the treatment of TOR1A dystonia.

Total Content of Piperidine Analysis in Artane by RP-HPLC Using Pre-Column Derivatization with 4-Toluene Sulfonyl Chloride.

A simple, sensitive and accurate reversed-phase high-performance liquid chromatography (RP-HPLC) method was established for the determination of piperidine and piperidine hydrochloride in artane, using pre-column derivatization with 4-toluenesulfonyl chloride. The RP-HPLC method was carried out on a Inertsil C18 column (250 × 4.6 mm I.D.) maintained at 30°C. The mobile phase consisted of water with 0.1% phosphoric acid (phase A) and acetonitrile (phase B) (32:68, V:V) at a flow rate of 1.0 mL/min. Linearity of piperidine was found in the range of 0.44-53.33 µg/mL with R2 = 0.9996. The limit of detection was estimated to be 0.15 µg/mL, and the limit of quantitation was 0.44 µg/mL. The average recovery was 101.82% with relative standard deviations of 0.6% at three spiked levels. The developed method using HPLC-ultraviolet system was a rapid tool for routine analysis of piperidine in the bulk form with good accuracy.

Central inhibition prevents the in vivo acute toxicity of harmine in mice.

BACKGROUND: Harmine is a ß-carboline alkaloid that displays antidepressant, antitumor and other pharmacological effects. However, the strong toxic effects limit its clinical application, and should be first considered. PURPOSE: To evaluate the in vivo toxicity of harmine and explore intervention strategies against its toxicity. METHODS: The in vivo toxicity of harmine was assessed from the symptoms, biochemical indices, and cardiovascular effects in mice. The intervention experiments were performed by using anesthetics, central drugs, and peripheral anticholinergics. RESULTS: The acute toxicity of harmine is significantly dose-dependent and the median lethal dose is 26.9 mg/kg in vivo. The typical symptoms include convulsion, tremor, jumping, restlessness, ataxia, opisthotonos, and death; it also changes cardiovascular function. The anesthetics improved the survival rate and abolished the symptoms after harmine poisoning. Two central inhibitors, benzhexol and phenytoin sodium, uniformly improved the survival rates of mice poisoned with harmine. The peripheral anticholinergics didn't show any effects. CONCLUSION: Harmine exposure leads to central neurological symptoms, cardiovascular effects and even death through direct inhibition of the central AChE activity, where the death primarily comes from central neurological symptoms and is cooperated by the secondary cardiovascular collapse. Central inhibition prevents the acute toxicity of harmine, and especially rapid gaseous anesthetics such as isoflurane, might have potential application in the treatment of harmine poisoning.

Centrally acting anticholinergic drug trihexyphenidyl is highly effective in reducing nightmares associated with post-traumatic stress disorder.

INTRODUCTION: Following a case study on scopolamine butyl bromide, an anticholinergic drug, we studied the effect of a central anticholinergic drug on post-traumatic stress disorder (PTSD)-related flashbacks and nightmares. METHODS: We administered trihexyphenidyl (TP) to 34 patients with refractory PTSD-related nightmares and flashbacks (open-label trial [n = 22]; single-blind trial [n = 12]), who had previously received psychiatric treatment for approximately 2-15 years, without therapeutic benefits. The effect of TP was determined using the Clinician-Administered PTSD Scale (CAPS) and the Impact of Event Scale-Revised (IES-R). RESULTS: Overall, most patients reported an improvement to none or mild on the CAPS for nightmares (88%) and flashbacks (79%). CONCLUSION: This study is the first to demonstrate the potential efficacy of TP in the treatment of refractory PTSD-related nightmares and flashbacks. Further double-blind, randomized control trials are needed to explore the potential clinical benefits of TP in PTSD.

Botulinum toxin type A versus anticholinergics for cervical dystonia.

BACKGROUND: This is an update of a Cochrane Review first published in 2005. Cervical dystonia is the most common form of focal dystonia and is a highly disabling movement disorder, characterised by involuntary, usually painful, head posturing. Currently, botulinum toxin type A (BtA) is considered the first line therapy for this condition. Before BtA, anticholinergics were the most widely accepted treatment. OBJECTIVES: To compare the efficacy, safety, and tolerability of BtA versus anticholinergic drugs in adults with cervical dystonia. SEARCH METHODS: We searched the Cochrane Movement Disorders' Trials Register to June 2003, screened reference lists of articles and conference proceedings to September 2018, and searched CENTRAL, MEDLINE, and Embase, with no language restrictions, to July 2020. SELECTION CRITERIA: Double-blind, parallel, randomised trials (RCTs) of BtA versus anticholinergic drugs in adults with cervical dystonia. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed records, selected included studies, extracted data using a paper pro forma, and evaluated the risk of bias and quality of the evidence. We resolved disagreements by consensus or by consulting a third review author. If enough data had been available, we were to perform meta-analyses using a random-effects model for the comparison of BtA versus anticholinergic drugs to estimate pooled effects and corresponding 95% confidence intervals (95% CI). The primary efficacy outcome was improvement in cervical dystonia-specific impairment. The primary safety outcome was the proportion of participants with any adverse event. MAIN RESULTS: We included one RCT of moderate overall risk of bias (as multiple domains were at unclear risk of bias), which included 66 BtA-naive participants with cervical dystonia. Two doses of BtA (Dysport; week 0 and 8; mean dose 262 to 292 U) were compared with daily trihexyphenidyl (up to 24 mg daily). The trial was sponsored by the BtA producer. BtA reduced cervical dystonia severity by an average of 2.5 points (95% CI 0.68 to 4.32) on the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) severity subscale 12 weeks after injection, compared to trihexyphenidyl. More participants reported adverse events in the trihexyphenidyl treatment group (76 events), compared with the BtA group (31 events); however, the difference in dropouts due to adverse events was inconclusive between groups. There was a decreased risk of dry mouth, and memory problems with BtA, but the differences were inconclusive between groups for the other reported side effects (blurred vision, dizziness, depression, fatigue, pain at injection site, dysphagia, and neck weakness). AUTHORS' CONCLUSIONS: We found very low-certainty evidence that BtA is more effective, better tolerated, and safer than trihexyphenidyl. We found no information on a dose-response relationship with BtA, differences between BtA formulations or different anticholinergics, the utility of electromyography-guided injections, or the duration of treatment effect.

A Novel Reduced Graphene Oxide Modified Carbon Paste Electrode for Potentiometric Determination of Trihexyphenidyl Hydrochloride in Pharmaceutical and Biological Matrices.

A novel promising carbon paste electrode with excellent potentiometric properties was prepared for the analysis of trihexyphenidyl hydrochloride (THP), the acetylcholine receptor and an anticholinergic drug in real samples. It contains 10.2% trihexyphenidy-tetraphenylborate ionic pair as the electroactive material, with the addition of 3.9% reduced graphene oxide and 0.3% of anionic additive into the paste, which consists of 45.0% dibutylphthalate as the solvent mediator and 40.6% graphite. Under the optimized experimental conditions, the electrode showed a Nernstian slope of 58.9 ± 0.2 mV/decade with a regression coefficient of 0.9992. It exhibited high selectivity and reproducibility as well as a fast and linear dynamic response range from 4.0 × 10-7 to 1.0 × 10-2 M. The electrode remained usable for up to 19 days. Analytical applications showed excellent recoveries ranging from 96.8 to 101.7%, LOD was 2.5 × 10-7 M. The electrode was successfully used for THP analysis of pharmaceutical and biological samples.

Pharmacological and neurosurgical interventions for individuals with cerebral palsy and dystonia: a systematic review update and meta-analysis.

AIM: To update a systematic review of evidence published up to December 2015 for pharmacological/neurosurgical interventions among individuals with cerebral palsy (CP) and dystonia. METHOD: Searches were updated (January 2016 to May 2020) for oral baclofen, trihexyphenidyl, benzodiazepines, clonidine, gabapentin, levodopa, botulinum neurotoxin (BoNT), intrathecal baclofen (ITB), and deep brain stimulation (DBS), and from database inception for medical cannabis. Eligible studies included at least five individuals with CP and dystonia and reported on dystonia, goal achievement, motor function, pain/comfort, ease of caregiving, quality of life (QoL), or adverse events. Evidence certainty was evaluated using GRADE. RESULTS: Nineteen new studies met inclusion criteria (two trihexyphenidyl, one clonidine, two BoNT, nine ITB, six DBS), giving a total of 46 studies (four randomized, 42 non-randomized) comprising 915 participants when combined with those from the original systematic review. Very low certainty evidence supported improved dystonia (clonidine, ITB, DBS) and goal achievement (clonidine, BoNT, ITB, DBS). Low to very low certainty evidence supported improved motor function (DBS), pain/comfort (clonidine, BoNT, ITB, DBS), ease of caregiving (clonidine, BoNT, ITB), and QoL (ITB, DBS). Trihexyphenidyl, clonidine, BoNT, ITB, and DBS may increase adverse events. No studies were identified for benzodiazepines, gabapentin, oral baclofen, and medical cannabis. INTERPRETATION: Evidence evaluating the use of pharmacological and neurosurgical management options for individuals with CP and dystonia is limited to between low and very low certainty. What this paper adds Meta-analysis suggests that intrathecal baclofen (ITB) and deep brain stimulation (DBS) may improve dystonia and pain. Meta-analysis suggests that DBS may improve motor function. Clonidine, botulinum neurotoxin, ITB, and DBS may improve achievement of individualized goals. ITB and DBS may improve quality of life. No direct evidence is available for oral baclofen, benzodiazepines, gabapentin, or medical cannabis.

Comparison of effectiveness of trihexyphenidyl and levodopa on motor symptoms in Parkinson's disease.

Despite anti-cholinergics being the oldest type of medication used for the treatment of Parkinson's disease (PD), the mechanism of action and exact benefit is unclear. This study compared the effectiveness of trihexyphenidyl (THP) and levodopa (LD) on motor symptoms in patients with PD. Patients with PD who are currently taking or had taken THP were recruited. UPDRS-III was done following overnight medication OFF state and 30 min, 60 min, 90 min, and 120 min after THP (4 mg). After a forty-eight-hour interval, UPDRS-III was assessed one hour after Levodopa/carbidopa (200/50 mg) in an overnight OFF state. Twenty patients with a mean age of 57.9 ± 7.8 years and mean duration of illness of 5.1 ± 3.6 years were recruited. UPDRS-III score reduction (%) with THP was maximum in the tremor sub-score (53.8 ± 22.8) and was significantly better compared to improvement in total-UPDRS-III (27.0 ± 14.7), bradykinesia-UPDRS-III (22.2 ± 27.2), rigidity-UPDRS-III (29.5 ± 28.0) and axial-UPDRS-III (8.1 ± 13.3) sub-score. In comparison, respective LD improvement was 67.1 ± 22.9 (tremor-UPDRS-III), 61.3 ± 14.4 (total-UPDRS-III), 67.9 ± 32.1 (bradykinesia-UPDRS-III), 65.3 ± 25.5 (rigidity-UPDRS-III) and 50.7 ± 16.0 (axial-UPDRS-III). Improvement (%) in tre-UPDRS-III post-THP was comparable to that of post-LD (53.8 ± 22.8 vs. 67.1 ± 22.9, p = 0.057). Those with same or better tremor response with THP had significantly milder baseline tremor severity than those who had better response with LD (tre-UPDRS-III-OFF, 10.0 ± 2.8 vs. 5.8 ± 4.0, p = 0.013). Both THP and LD showed significant improvement in UPDRS-III. With THP, the maximum degree of improvement was in the tremor sub-score and not significantly different to that obtained by LD. Those with better tremor response on THP had milder tremor severity.

Beneficial role of central anticholinergic agent in preventing the development of symptoms in mouse model of post-traumatic stress disorder.

Objectives The present study was designed to investigate the effectiveness of trihexyphenidyl, a central anticholinergic drug, in preventing the post-traumatic stress disorder (PTSD) symptoms in a mouse model. Methods Mice were subjected to underwater trauma stress for 30 s on day 1 followed by three situational reminders (3rd, 7th and 14th day). Thereafter, the behavioral alterations including freezing behavior were noted on 21st day. The serum corticosterone levels were measured as a biochemical marker of trauma. Elevated plus maze test was done on day 1 and day 2 to assess the memory formation following exposure to trauma. Results Trauma and situational reminders were associated with a significant development of behavioral changes and freezing behavior on the 21st day. Moreover, there was also a significant decrease in the serum corticosterone levels. A single administration of trihexyphenidyl (2 and 5 mg/kg) significantly restored trauma associated-behavioral changes and serum corticosterone levels. Moreover, it significantly increased the transfer latency time on day 2 following stress exposure in comparison to normal mice suggesting the inhibition of memory formation during trauma exposure. Trihexyphenidyl also led to significant reduction in freezing behavior in response to situational reminders again suggesting the inhibition of formation of aversive fear memory. Conclusion The blockade of central muscarinic receptors may block the formation of aversive memory during the traumatic event, which may be manifested in form of decreased contextual fear response during situational reminders. Central anticholinergic agents may be potentially useful as prophylactic agents in preventing the development of PTSD symptoms.

Trihexyphenidyl induced malignant hyperthermia in a patient with Parkinson's disease complicated with pneumonia: A case report.

INTRODUCTION: Drug-induced fever is easy to overlook in respiratory departments. High fever is a rare side effect of trihexyphenidyl, which can be used clinically to treat Parkinson's disease. Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a group of clinical syndromes caused by various diseases, resulting in water retention and refractory hyponatremia. However, pneumonia combined with malignant hyperthermia and SIADH has rarely been reported. We describe an unusual case of malignant hyperthermia and refractory hyponatremia due to trihexyphenidyl adverse reaction. PATIENT CONCERNS: Fifty-five-year-old male with pneumonia presented with malignant hyperthermia and refractory hyponatremia has a history of Parkinson's disease. DIAGNOSIS: Early considerations related the described hyperthermia findings to the manifestations of pneumonia. However, the last findings were due to trihexyphenidyl adverse reaction. INTERVENTIONS: Broad-spectrum antibiotics, oral and intravenous supplement of concentrated sodium chloride, drug, and physical cooling. OUTCOMES: The patient survived. During the 3-month follow up, the patient was no recurrence of fever or hyponatremia. CONCLUSION: High fever and SIADH can be a rare adverse reaction to trihexyphenidyl. Therefore, possible drug factors should be considered in the case. Consideration of other possible causes can improve early diagnosis and treatment of patients with fever of unknown origins.