- [Similarity of Clinically Significant Neuropsychiatric Adverse Reactions Listed in Package Inserts between the Anti-influenza Drugs Oseltamivir and Amantadine (Possibility Attributable to Common Pharmacological Effects)]. [Journal Article]
- YZYakugaku Zasshi 2018 Sep 01; 138(9):1201-1215
- The anti-influenza virus drug oseltamivir has been reported to have several pharmacological actions including blocking of nicotinic acetylcholine receptor channels and activation of the dopaminergic...
The anti-influenza virus drug oseltamivir has been reported to have several pharmacological actions including blocking of nicotinic acetylcholine receptor channels and activation of the dopaminergic system. These pharmacological actions highly overlap those of amantadine, another anti-influenza virus drug authorized in Japan, and ester-type local anesthetics. Moreover, oseltamivir and amantadine can clinically induce similar adverse neuropsychiatric reactions. In the present study, from the database of the Pharmaceuticals and Medical Devices Agency (PMDA), we surveyed 2576 drugs for which neuropsychiatric side effects similar to those of oseltamivir, amantadine and local anesthetics (abnormal behavior, confusion, consciousness disturbance, convulsion, delirium, delusion, hallucination, myoclonus, tremor) are listed as "clinically significant adverse reactions", and found 327 that had at least one of these adverse reactions. Other neuraminidase inhibitors (laninamivir, peramivir and zanamivir) did not elicit such adverse reactions. By discussing the pharmacological effects of drugs that elicit these adverse reactions, we propose that the similarity of adverse neuropsychiatric reactions between oseltamivir and amantadine is possibly attributable to their common pharmacological effects.
- Trihexyphenidyl for dystonia in cerebral palsy. [Review]
- CDCochrane Database Syst Rev 2018 May 15; 5:CD012430
- CONCLUSIONS: At present, there is insufficient evidence regarding the effectiveness of trihexyphenidyl for people with cerebral palsy for the outcomes of: change in dystonia, adverse effects, increased upper limb function and improved participation in activities of daily living. The study did not measure pain or quality of life. There is a need for larger randomised, controlled, multicentre trials that also examine the effect on pain and quality of life in order to determine the effectiveness of trihexyphenidyl for people with cerebral palsy.
- Experimental Intrastriatal Applications of Botulinum Neurotoxin-A: A Review. [Review]
- IJInt J Mol Sci 2018 May 07; 19(5)
- Parkinson’s disease (PD) is one of the most frequent neurodegenerative disorders. Its main pathophysiological characteristic is the loss of dopaminergic neurons in the substantia nigra pars com...
Parkinson’s disease (PD) is one of the most frequent neurodegenerative disorders. Its main pathophysiological characteristic is the loss of dopaminergic neurons in the substantia nigra pars compacta followed by a lack of striatal dopaminergic input and a consequent disinhibition of tonically active cholinergic interneurons. The resulting striatal hypercholinism causes major motor symptoms in PD. Anticholinergic pharmacotherapies have antiparkinsonian effects on motor symptoms, but, due to systemic actions, also numerous severe side effects occur on a regular basis. To circumvent these side effects, a local anticholinergic therapy acting exclusively in the striatum would be reasonable. Botulinum neurotoxin-A (BoNT-A) is synthesized by Clostridium botulinum and blocks the release of acetylcholine from the presynaptic bouton. For several decades, BoNT-A has been used successfully for medical and cosmetic purposes to induce controlled paralyses of single muscles. Our group and others investigated the experimental treatment of striatal hypercholinism by the direct injection of BoNT-A into the striatum of rats and mice as well as of hemiparkinsonian animal models. This review gives an overview of the most important results of the experimental intrastriatal BoNT-A application, with a focus on hemiparkinsonian rats.
- Anticholinergic drugs and risk of dementia: case-control study. [Journal Article]
- BMJBMJ 2018 Apr 25; 361:k1315
- CONCLUSIONS: A robust association between some classes of anticholinergic drugs and future dementia incidence was observed. This could be caused by a class specific effect, or by drugs being used for very early symptoms of dementia. Future research should examine anticholinergic drug classes as opposed to anticholinergic effects intrinsically or summing scales for anticholinergic exposure.
- Misuse of Trihexyphenidyl (Artane) on Réunion Island. [Journal Article]
- JCJ Clin Psychopharmacol 2018; 38(3):250-253
- CONCLUSIONS: This cohort describing the clinical characteristics of 69 patients is the largest cohort studied for THP addiction. Patients from the Centres for Addiction Prevention and Treatment were the youngest and most recently addicted, whereas general practice patients had been addicted for longer and were more socially integrated. This clinical description of THP addiction therefore enables us to identify the patients who are the most at risk, to set up an adapted care protocol.
- Pharmacological interventions for treating sialorrhea associated with neurological disorders: A mixed treatment network meta-analysis of randomized controlled trials. [Review]
- JCJ Clin Neurosci 2018; 51:12-17
- Sialorrhea is a common distress associated with certain neurological disorders. The aim of this study is to compare the pharmacological agents used for treating sialorrhea by network meta-analysis. E...
Sialorrhea is a common distress associated with certain neurological disorders. The aim of this study is to compare the pharmacological agents used for treating sialorrhea by network meta-analysis. Electronic databases were searched for randomized clinical trials comparing active drugs with either placebo or other active drugs. Total drooling scores was the primary outcome measure. Inverse variance heterogeneity model was used for both direct and mixed treatment comparison analysis. Twenty one studies were included in the systematic review and 15 in the meta-analysis. Compared to placebo, benztropine, botulinum toxins A and B are associated with a significant reduction in the frequency and severity of drooling both in the overall neurological disorders as well as for children with cerebral palsy. Only botulinum toxin A and B were associated with significant therapeutic effects in Parkinson's disease. Benztropine and botulinum toxins A and B were observed to be effective in reducing sialorrhea associated with neurological disorders.
- 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.
- Anticholinergic medication for antipsychotic-induced tardive dyskinesia. [Review]
- CDCochrane Database Syst Rev 2018 01 17; 1:CD000204
- CONCLUSIONS: Based on currently available evidence, no confident statement can be made about the effectiveness of anticholinergics to treat people with antipsychotic-induced tardive dyskinesia. The same applies for the withdrawal of such medications. Whether the withdrawal of anticholinergics may benefit people with antipsychotic-induced TD should be evaluated in a parallel-group, placebo-controlled randomised trial, with adequate sample size and at least 6 weeks of follow-up.
- The effect of intravitreal cholinergic drugs on motor control. [Journal Article]
- BBBehav Brain Res 2018 Feb 26; 339:232-238
- The retina bears embryological, neurochemical and functional similarities to the circadian and dopamine systems of the brain. Recent studies have shown that the intravitreal injection of minute quant...
The retina bears embryological, neurochemical and functional similarities to the circadian and dopamine systems of the brain. Recent studies have shown that the intravitreal injection of minute quantities of L-dopa and of the melatonin receptor antagonist ML-23 have anti-Parkinsonian potential. Furthermore, it has been suggested that light therapy may be potentially useful in treating some aspects of Parkinson's disease (PD) and it is hypothesized that this treatment works via the circadian system. Given that little is known about the mechanism by which such treatments work the present study was designed to examine the role of the acetyl cholinergic system of the retina in gross bodily movement. While IVIT atropine was shown to improve movement in intact rats Cogentin treated rats showed impairment of motor function compared to control rats or to rats treated with any other cholinergic drug. Furthermore, a link between the phase of the light/dark cycle and the efficacy of these drugs in altering movement was demonstrated. These results show that anticholinergic systems in the retina can exert control over movement which has been solely attributed to the function of deep brain structures.
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- Modification of the natural progression of epileptogenesis by means of biperiden in the pilocarpine model of epilepsy. [Journal Article]
- EREpilepsy Res 2017; 138:88-97
- Brain injuries are often associated with the later development of epilepsy. Evidence suggests that morphological and functional changes occur in the remaining neural tissue during a silent (or latent...
Brain injuries are often associated with the later development of epilepsy. Evidence suggests that morphological and functional changes occur in the remaining neural tissue during a silent (or latent) period in which no seizures are expressed. It is believed that this silent (reorganization) period may provide a therapeutic window for modifying the natural history of disease progression. Here we provide evidence that biperiden, a muscarinic anticholinergic agent, is able to alter disease progression in an animal model of epilepsy. We observed that biperiden was capable of slowing the manifestation of the first spontaneous epileptic seizure and effectively reduced the severity and number of recurrent, spontaneous epileptic seizures during the animals' lifespan. Biomolecular (microdialysis) and electrophysiological (extracellular field recordings) studies determined that biperiden was capable of elevating the threshold of hippocampal excitability, thereby making the hippocampal glutamatergic pathways less responsive to stimuli when high concentrations of potassium were used in vivo or in vitro. Notably, there was no hindrance of long-term memory or learning (a potential problem given the amnestic nature of biperiden). We conclude that biperiden has antiepileptogenic potential and may represent an opportunity for the prevention of post-traumatic epilepsy.