Milameline (hydrochloride)

Milameline (CI 979; RU35926) hydrochloride is a nonselective, partical and orally active muscarinic receptor agonist that improves cognition. Milameline hydrochloride 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 hydrochloride has a higher affinity for sites [³H]CMD (IC₅₀ = 20 nM), than [³H]QNB, (IC₅₀ = 3059 nM). Milameline hydrochloride produces both central and peripheral cholinergic effects and reverses the cognitive deficits induced by Scopolamine (HY-N0296). Milameline hydrochloride can be used for the study of Alzheimer’s Disease^[1]. In Vitro:Milameline hydrochloride increases soluble APP (sAPP) secretion in CHO cells transfected with human M1 or M3 receptors^[1].
In Vivo:Milameline (0.2 mg/kg (rat), p.o., or 0.01 mg/kg (monkey), i.m., single dose) hydrochloride 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.) hydrochloride 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 hydrochloride increases cerebral blood flow in rats, and its distribution in the brain is consistent with the areas where the cholinergic system is enriched^[1].