title: Ethylatropine Bromide as a Peripherally Restricted Muscarinic Antagonist.
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.
authors.affiliation: Department of Pharmacology, Emory University , 1510 Clifton Road NE, Atlanta, Georgia 30322, United States.
authors.forename: Asheebo
authors.identifier: 0000-0003-0895-0839
authors.initials: A
authors.lastname: Rojas
authors.affiliation: Department of Pharmacology, Emory University , 1510 Clifton Road NE, Atlanta, Georgia 30322, United States.
authors.forename: Thota
authors.initials: T
authors.lastname: Ganesh
authors.affiliation: Department of Pharmacology, Emory University , 1510 Clifton Road NE, Atlanta, Georgia 30322, United States.
authors.forename: Alec
authors.initials: A
authors.lastname: Walker
authors.affiliation: Department of Pharmacology, Emory University , 1510 Clifton Road NE, Atlanta, Georgia 30322, United States.
authors.forename: Raymond
authors.initials: R
authors.lastname: Dingledine
mesh_terms: D000818:Animals; D001286:Atropine Derivatives / Q000494:pharmacology*; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018721:Muscarinic Agonists / Q000633:toxicity; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D010862:Pilocarpine / Q000633:toxicity
chemical_list: D001286:Atropine Derivatives; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D010862:Pilocarpine
keywords: M1; Muscarinic receptor; acetylcholine; atropine; calcium; carbachol; ethylatropine; methylatropine; nicotinic receptor; pilocarpine; salivation; α7