Effects of melatonin
These are three melatonin receptors. MT1 is present in the SCN and the pars tuberalis of the pituitary gland, and inhibits the wake promoting effect of the SCN and influences endocrine funtion. MT2 is present in the SCN and the retina and can entrain the SCN. The role of the MT3 receptor is uncertain.

Melatonin binds to calmodulin within the cells, but the details of its biochemical effects are unclear.
Its main actions are as follows.

Effects on SCN
Melatonin appears to have two effects on the SCN which are mediated either by a direct effect on the circadian rhythm generating cells or by activation of GABA-ergic neurones within the SCN which inhibit its activity (

Fig. 2.7). First, it entrains the SCN, modifying the timing of its circadian rhythms and reducing body temperature, predisposing towards NREM rather than REM sleep and influencing the timing of sleep.

This action is greatest in the evening when the circadian drive to wakefulness is strongest. It causes a phase advance of the sleep pattern with opening of the ‘gate’ for sleep through loss of the normal ‘wakefulness maintenance zone’ shortly before the usual sleep time.

Secondly, melatonin may synchronize other circadian rhythms, such as temperature and cortisol secretion, either through an action on the SCN or directly on the centres controlling these rhythms. The sleep and temperature rhythms, for instance, can be dissociated either because of incoordination of subpopulations of cells in the SCN which control the two rhythms, or through divergences in the mechanisms controlling them outside the SCN.