Abstract：
:Quaternary ammonium analogues of atropine that are unable to cross the blood-brain barrier are used to alleviate peripheral muscarinic toxicity in animal models of epilepsy produced by systemic administration of pilocarpine or diisopropylfluorophosphate (DFP). Currently, methylatropine is the most popular and potent of these quaternary derivatives; however, it is expensive and produced in limited quantity. Here, we propose the use of ethylatropine bromide as an alternative to methylatropine. The synthesis of ethylatropine bromide is simple, inexpensive and has low environmental impact. We demonstrate the efficacy of ethylatropine bromide to antagonize the carbachol induced rise in intracellular calcium in a calcium mobilization assay, and its ability to prevent pilocarpine-induced total fluid secretions in mice without blocking pilocarpine-induced seizures. The ease of synthesis, cost effectiveness, and efficacy makes ethylatropine bromide a desirable alternative to methylatropine as a peripherally restricted acetylcholine receptor antagonist.
journal_name
ACS Chem Neuroscijournal_title
ACS chemical neuroscienceauthors
Rojas A,Ganesh T,Walker A,Dingledine Rdoi
10.1021/acschemneuro.6b00334subject
Has Abstractpub_date
2017-04-19 00:00:00pages
712-717issue
4issn
1948-7193journal_volume
8pub_type
杂志文章abstract：:Pharmaceutical companies assessing the nervous system effects of candidate therapeutics often use a behavioral assay in rodents that assesses the drug's subjective (internal stimulus) effects. Variants of this so-called "drug discrimination task" have also been widely used by basic scientist for more than 50 years to ...
journal_title：ACS chemical neuroscience
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journal_title：ACS chemical neuroscience
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journal_title：ACS chemical neuroscience
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journal_title：ACS chemical neuroscience
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