M-II has weak affinity for the serotonin 5-HT2B receptor, but no appreciable affinity for other receptors or enzymes. Similar to ramelteon, M-II does not interfere with the activity of a number of endogenous enzymes.Ramelteon has no appreciable affinity for the GABA receptors or for receptors that bind neuropeptides, cytokines, serotonin, dopamine, noradrenaline, acetylcholine, and opioids. Ramelteon also does not interfere with the activity of a number of selected enzymes in a standard panel. Mechanism of action
The activity of ramelteon at the MT1 and MT2 receptors is believed to contribute to its sleep-promoting properties, as these receptors, acted upon by endogenous melatonin, are thought to be involved in the maintenance of the circadian rhythm underlying the normal sleep–wake cycle. Pharmacokinetics
Absorption
The total absorption of ramelteon is 84% while its oral bioavailability is 1.8%. The low bioavailability of ramelteon is due to extensive first-pass metabolism. The absorption of ramelteon is rapid, with peak levels being reached after approximately 0.75 hours (range 0.5–1.5 hours). Food increases peak concentrations of ramelteon by 22% and overall exposure by 31% and delays the time to peak levels by approximately 0.75 hours. The pharmacokinetics of ramelteon are linear across a dose range of 4 to 64 mg. There is substantial interindividual variability in the peak concentrations and area-under-the-curve levels of ramelteon which is consistent with high first-pass metabolism. Distribution
The volume of distribution of ramelteon is 73.6 L, which suggests substantial tissue distribution. The plasma protein binding of ramelteon is 82% independently of concentration. Ramelteon is primarily bound to albumin (70%).
of women without a history of reproductive problems found that about 5% of women had an arcuate uterus when they defined an arcuate uterus any fundal protrusion into the cavity that had an apical angle of more than 90 degrees. Accordingly, it was the most common uterine anomaly, followed by septate uterus (3%) and bicornuate uterus (0.5%). References


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