ABSTRACT
Ramelteon is the first Food and Drug Administration (FDA)-approved agent believed to act by mimicking the effects of the hormone melatonin (Figure 34.1). It does so, as described below, by combining with and activating melatonin’s MT1 and MT2 receptors in the brain, which may mediate melatonin’s sleep-promoting effects following its secretion from the pineal gland.1-8 When melatonin is administered to young adults during the daytime or early evening (for example, to those initiating eastbound travel, or undertaking shift work) it promotes sleep onset;4,9 when given at bedtime to older adults who suffer from prolonged nocturnal awakenings, it improves sleep efficiency and increases sleep time.6,10 The fully effective oral dose of melatonin (0.2-0.5 mg, usually 0.3 mg4,6) is the same for both uses, and is equal to the amount needed to elevate plasma melatonin levels to what they would normally be, during the night, in young adults (about 100-200 pcg/ml, up from 2-10 pcg/ml around noon). Among older people whose substantially calcified pineals secrete less of the hormone, nocturnal plasma melatonin levels may only rise to 25-50 pcg/ml;11-14
this deficiency apparently underlies their impairment in sleep efficiency6 and their hypnotic response to physiological doses of melatonin.
