Clemastine induces an impairment in developmental myelination

Abnormalities in myelination are associated to behavioral and cognitive dysfunction in neurodevelopmental psychiatric disorders. Thus, therapies to promote or accelerate myelination could potentially ameliorate symptoms in autism. Clemastine, a histamine H1 antagonist with anticholinergic properties against muscarinic M1 receptor, is the most promising drug with promyelinating properties (Mei et al., 2014). Clemastine penetrates the blood brain barrier efficiently and promotes remyelination in different animal models of neurodegeneration including multiple sclerosis, ischemia and Alzheimer's disease. However, its role in myelination during development is unknown. We showed that clemastine treatment during development increase oligodendrocyte differentiation in both white and gray matter. However, despite the increase in the number of oligodendrocytes, conduction velocity of myelinated fibers of corpus callosum decreased in clemastine-treated mice. Confocal and electron microscopy showed a reduction in the number of myelinated axons and nodes of Ranvier and a reduction of myelin thickness in corpus callosum. To understand the mechanisms leading to myelin formation impairment in the presence of an excess of myelinating oligodendrocytes, we focused on microglial cells which also express muscarinic M1 receptors. Importantly, the population of CD11c+ microglia cells, necessary for myelination, as well as the levels of insulin growth factor-1 decrease in clemastine-treated mice. Altogether, these data suggest that clemastine impact on myelin development is more complex than previously thought and could be dependent on microglia-oligodendrocyte crosstalk. Further studies are needed to clarify the role of microglia cells on developmental myelination.

Innovative Method Development Comprehensive Separation of Impurities and Validation for a novel Antipsychotic Drug Blonanserin

Blonanserin an antipsychotic novel drug used for the treatment of schizophrenia has antagonist properties for dopamine D2 and serotonin 5-HT2. On the other hand, it lacks adrenergic-α1, muscarinic M1, and histamine H1 antagonist activities. Clinical studies demonstrated in Japan had shown to be more effective for treating negative as well as positive schizophrenic symptoms. This drug was accepted and approved worldwide in the treatment of schizophrenia. A new HPLC method was developed and validated for the estimation of Impurities of Blonanserin (BNS) to ensure that the methodology meets the requirements of the target analysis application. Active and efficient chromatographic separation was achieved on a Zorbax Bonus RP EP C18 column having a particle size of 5μm, with dimensions of 250mm × 4.6 mm, mobile phase containing pH 2.4 buffer and Organic, with 1.0 ml /min flow rate, column oven temperature at 30oC and the eluent detection at 245 nm. The method shows well-separated impurities, is specific without interference from blank solution with resolution more than 1.2 between any of the impurity, correlation coefficient more than 0.99 showing good linearity; mean recovery ranging from 97% to 105% and is very sensitive at lower detection and quantification limits. This method was well developed and has been applied successfully to monitor and estimate impurities in Blonanserin.

Rhinorrhea as a Result of Alzheimer's Disease Treatment: A Case Report

This report describes a case of persistent rhinorrhea caused by donepezil and successfully treated with azelastine in an 84-year-old male treated with donepezil for Alzheimer's disease (AD) who experienced excessive rhinorrhea. After initiation of donepezil for AD the patient showed increased discomfort with rhinorrhea. A trial with an oral second-generation antihistamine provided no benefit. Azelastine 0.1% nasal spray was initiated and successfully reduced the rhinorrhea. A less-oftenreported side effect of donepezil that may impact patients is rhinorrhea, also described as rhinitis or nasopharyngitis.<br/> Cholinergic mechanisms of rhinorrhea have been previously described in the condition of vasomotor rhinitis and are not allergy-mediated though symptomatology overlaps. Azelastine is a histamine H1 antagonist indicated for vasomotor rhinitis. To our knowledge there are no previous descriptions in the literature that recommend azelastine to manage symptoms of rhinorrhea caused by treatments for AD. The adverse side effect of rhinorrhea, resulting from treatment with donepezil, can be disregarded as allergy symptoms. Instead, a trial of azelastine 0.1% nasal spray, one spray each nostril daily then titrated up to two sprays in each nostril twice daily as tolerated, may be warranted. Patients and caregivers should be aware of epistaxis as a potential side effect of azelastine, especially for patients on antithrombotic therapy.

A Concise and Efficient Synthesis of an Impurity, N-Desmethyl Alcaftadine from Alcaftadine: An H1 Antagonist

Herein, a simple approach for the synthesis of N-desmethyl alcaftadine, an H1 histamine antagonist in solid state and its structure is presented. The reactions were performed under mild and metal free conditions at reflux temperature within a range of 65-70 ºC and the desired product N-desmethyl alcaftadine was obtained in high purity with good yield (96.42 %). It was detected by ultra-high-performance liquid chromatography (UHPLC).

Acute and subchronic effects of bilastine (20 and 40 mg) and hydroxyzine (50 mg) on actual driving performance in healthy volunteers

Bilastine is a new second-generation H1 antagonist. Although bilastine has been demonstrated to produce little or no performance impairment in laboratory tests, it cannot be excluded that it produces impairments in real-life performance such as driving. This study aims to assess the effects of two doses of bilastine (20 and 40 mg) on actual driving after single and repeated administration. Hydroxyzine 50 mg was included as an active control. Twenty-two particpants (11 females, 11 males) were tested in a placebo-controlled, randomized, double-blind, four-way cross-over design. Participants were treated with once-daily doses for eight consecutive days. On day 1 and 8 of each treatment period participants performed an actual highway driving test. The primary variable was standard deviation of lateral position (SDLP), a measure of weaving. Results demonstrated that hydroxyzine significantly increased SDLP on days 1 and 8 of treatment. Bilastine did not affect SDLP. It is concluded that hydroxyzine produces severe driving impairment after single doses and that this impairment only partly mitigates over time due to a lack of complete tolerance. Bilastine did not produce any driving impairment after single and repeated doses and can be safely used in traffic in doses up to 40 mg.