Roserem (Ramelteon) 8 mg 100 tablets

Ramelteon is a melatonin receptor agonist with high affinity for the MT1 and MT2 melatonin receptors and selectivity for the MT3 receptor. Ramelteon exhibits full agonist activity in vitro in cells expressing human MT1 and T2 receptors, and high selectivity for human MT1 and MT2 receptors over the MT3 receptor. Ramelteon's activity at the MT1 and MT2 receptors is thought to underlie its sleep-related properties, as these receptors are mediated by endogenous melatonin, which is involved in maintaining the circadian rhythm underlying the normal sleep-wake cycle. Ramelteon has no detectable affinity for the GABA receptor complex (gamma-aminobutyric acid receptors) or receptors that bind neuropeptides, cytokines, serotonin, dopamine, norepinephrine, acetylcholine, and opiates. Ramelteon also does not interfere with the activity of certain other enzymes.

The practical significance of Ramelteon's lack of affinity for the MT3 receptor, despite the fact that the manufacturers emphasize this fact in their advertising, is not yet clear. The MT3 receptor is present exclusively in the intestine and may have no relation to sleep or wakefulness at all.

Ramelteon's main metabolite, M-II, is active and its parent molecule has about one-tenth and one-fifth the affinity for human MT1 and MT2 receptors, respectively, and is 17 to 25 times less potent than Ramelteon. Although M-II has lower potency at the MT1 and MT2 receptors than the parent drug, M-II circulates at higher concentrations than ramelteon and has systemic effects on the body, unlike ramelteon. M-II has weak affinity for the serotonin 5-HT2B receptors, and no significant affinity for other receptors or enzymes. Like ramelteon, M-II does not interfere with the activity of a number of endogenous enzymes.

All other known metabolites of ramelteon are inactive.

There are no published studies comparing the safety and efficacy of ramelteon and the hormone it mimics, melatonin. Melatonin is a much cheaper and more widely available drug, available over the counter in the US and Canada. Melatonin has the same biological effects on the body as ramelteon. Studies have been conducted to compare the properties of Ramelteon and melatonin in cats, and it has been shown that Ramelteon has a significantly (3 times) longer lasting effect and influence on the EEG in sleeping cats.

In a double-blind multicenter study, Ramelteon was shown to reduce the time to fall asleep by approximately 15-20 minutes, when taken at doses of 8 mg and 16 mg after four weeks compared to placebo (29-32 minutes instead of 48). The total sleep time reached 40 minutes, which was identical to placebo. Patients taking Ramelteon reported a subjective feeling of a much longer period of sleep than those taking placebo. Ramelteon, compared to placebo, has a much faster onset of action: one or two weeks. However, with a period of four weeks, the results are approximately equivalent to placebo.

Manufactured by Takeda (Japan)