Demecarium Bromide is the bromide salt form of demecarium, a quaternary ammonium compound and a long-acting cholinesterase inhibitor with parasympathomimetic activity. When used topically, demecarium inactivates both pseudocholinesterase and acetylcholinesterase, thereby preventing acetylcholine breakdown and increasing acetylcholine activity. This causes contraction of the iris sphincter muscle (producing miosis) and the ciliary muscle (affecting the accommodation reflex). In so doing, this agent increases the outflow of the aqueous humor, thereby reducing intraocular pressure.
Demecarium ligand of proteins in family: ACHE, BCHE
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Title: The effects of topical ocular application of 0.25% demecarium bromide on serum acetylcholinesterase levels in normal dogs Ward DA, Abney K, Oliver JW Ref: Vet Ophthalmol, 6:23, 2003 : PubMed
OBJECTIVE: To assess the effects of topical ocular application of 0.25% demecarium bromide on serum acetylcholinesterase (AChE) levels in normal dogs. ANIMALS: Nine adult mixed breed dogs weighing between 18 and 27 kg. PROCEDURES: Fifty micro L of 0.25% demecarium bromide were applied to one eye of each dog every 8 h for 6 days. Blood was analyzed for AChE levels prior to commencement of eye drops, and at 45 min, 1 h 45 min, 4 h 45 min, 1 day, 3 days, and 7 days following commencement of eye drops using a 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB) reaction. RESULTS: Acetylcholinesterase levels declined over the first 24 h following commencement of demecarium administration in most dogs. This decline was highly variable and was statistically significant by 24 h. In some individuals AChE levels were suppressed to levels approaching clinical toxicity. By day 3 AChE levels had risen to levels above baseline in most dogs. CONCLUSIONS: Topical ocular application of demecarium causes transient suppression of systemic acetylcholinesterase levels in most dogs. Acetylcholinesterase levels generally do not fall to toxic levels, but may do so in certain individuals. Demecarium bromide eye drops generally do not cause AChE toxicity, but dogs receiving such therapy should be monitored for signs of AChE toxicity, and concomitant use of other AChE inhibitors should be avoided.
Title: Activation and blockade of cardiac muscarinic receptors by endogenous acetylcholine and cholinesterase inhibitors Brown JH, Wetzel GT, Dunlap J Ref: Journal of Pharmacology & Experimental Therapeutics, 223:20, 1982 : PubMed
Cholinesterase inhibitors are known to potentiate the effects of acetylcholine (ACh) and vagal stimulation on the myocardium. The studies presented here demonstrate that cholinesterase inhibitors (ChEI) also have activity in isolated atria in the absence of extrinsic cholinergic stimulation and that, depending on the ChEI, either indirect stimulation or direct blockade of cardiac muscarinic receptors can occur. Muscarinic agonists inhibit cyclic AMP formation in atria and the ChEIs physostigmine, neostigmine and echothiophate likewise produce a marked attenuation of isoproterenol-stimulated cyclic AMP accumulation The effect of physostigmine appears to result from muscarinic receptor activation by endogenous ACh as it is blocked by atropine. In contrast, the ChEI ambenonium does not stimulate but instead blocks muscarinic receptors coupled to cyclic AMP accumulation. Radioligand binding studies provide direct evidence that both ambenonium and demecarium are relatively potent muscarinic receptor antagonists, whereas physostigmine and other ChEI have little direct receptor activity. Physostigmine and ambenonium also have different effects on heart rate in vivo, the former potentiating and the latter apparently blocking vagal tone. The inhibition of cyclic AMP formation produced by physostigmine can be used as a measure of the concentration of endogenous ACh available at muscarinic receptor sites. Physostigmine blocks cyclic AMP formation in atria incubated in the absence of calcium or in the presence of tetrodotoxin, suggesting that endogenous ACh is spontaneously released in the absence of neuronal activity or depolarization-secretion coupling.
