Milameline (CI 979; RU35926) hydroiodide is a nonselective, partical and orally active muscarinic receptor agonist that improves cognition. Milameline hydroiodide has equal affinity for different subtypes of human muscarinic receptors with IC50 of 1.3 µM for M1-, 1.1 µM for M2-, 1.5 µM for M3-, and 1.9 µM for M4-muscarinic receptors. Milameline hydroiodide has a higher affinity for sites [ 3 H]CMD ( IC50 = 20 nM), than [ 3 H]QNB, ( IC50 = 3059 nM). Milameline hydroiodide produces both central and peripheral cholinergic effects and reverses the cognitive deficits induced by Scopolamine. Milameline hydroiodide can be used for the study of Alzheimer’s Disease [1].
In Vivo, Milameline (0.2 mg/kg (rat), p.o., or 0.01 mg/kg (monkey), i.m., single dose) hydroiodide produces central effects (hypothermia) in rats and central cholinergic effects in monkeys (increased neocortical arousal in the electroencephalogram (EEG))[1]. Milameline (0.02- > 0.1 mg/kg, p.o.) hydroiodide effectively reverses scopolamine-induced working memory impairment in rats at low doses (0.02-0.1 mg/kg), but the effect is reduced at high doses (> 0.1 mg/kg)[1]. Milameline hydroiodide increases cerebral blood flow in rats, and its distribution in the brain is consistent with the areas where the cholinergic system is enriched[1].
In Vitro, Milameline hydroiodide increases soluble APP (sAPP) secretion in CHO cells transfected with human M1 or M3 receptors[1].
References:
[1]. Heidrich, A., and M. Rösler. "Milameline hydrochloride: nonselective, partial muscarinic receptor agonist for the treatment of Alzheimer's disease?." CNS Drug Reviews (1999).
In Vivo, Milameline (0.2 mg/kg (rat), p.o., or 0.01 mg/kg (monkey), i.m., single dose) hydroiodide produces central effects (hypothermia) in rats and central cholinergic effects in monkeys (increased neocortical arousal in the electroencephalogram (EEG))[1]. Milameline (0.02- > 0.1 mg/kg, p.o.) hydroiodide effectively reverses scopolamine-induced working memory impairment in rats at low doses (0.02-0.1 mg/kg), but the effect is reduced at high doses (> 0.1 mg/kg)[1]. Milameline hydroiodide increases cerebral blood flow in rats, and its distribution in the brain is consistent with the areas where the cholinergic system is enriched[1].
In Vitro, Milameline hydroiodide increases soluble APP (sAPP) secretion in CHO cells transfected with human M1 or M3 receptors[1].
References:
[1]. Heidrich, A., and M. Rösler. "Milameline hydrochloride: nonselective, partial muscarinic receptor agonist for the treatment of Alzheimer's disease?." CNS Drug Reviews (1999).