A number of melatonin agonists have been approved for use or are in various phases of clinical trials. An agonist is a substance that mimics the body’s own regulatory function, by binding to the cell receptor and stimulating normal function. Since melatonin has a short half-life, scientists have developed prolonged release formulations to provide melatonin throughout the sleep period to maintain sleep throughout the night. These new melatonin agonists are synthetic formulations of melatonin with a longer half-life than natural melatonin. All of the following medications have shown to be effective in improving sleep quality.

Ramelteon (brand name Rozerem) has been approved by the Food and Drug Administration for use in the United States. Ramelteon reduces the amount of time needed to fall asleep and increases the length of sleep, and is especially effective for treating insomnia in the elderly. Balance, mobility or memory are not affected if an elder gets up during the middle of the night. Side effects are mild; and ramelteon has no affect upon alertness, there is no “hangover,” and no withdrawal symptoms. Ramelteon is probably the most notable and successful chronobiotic to date aside from melatonin.

Agomelatine (brand name Valdoxan) is an antidepressant in the final phase of approval for clinical use in the United States. Valdoxan improves sleep in people with depression; this then improves the depression symptoms. This drug is effective for the treatment of SAD and may also be useful in treating seasonal weight gain. Valdoxan is tolerated well, with no behavioral changes, no dependence, and no “hangover.” Valdoxan needs safety studies to determine the effect of its use over a long period of time. (Agomelatine has been used as an example of how some new medicines are subject to publication bias - where the promoters punish only positive test results and do not publish ones that show the drug has little or no benefit.)

Circadin ™ (prolonged-release melatonin 2 mg) has been approved by the European Medicines Agency for the treatment of insomnia. Melatonin is released over a period of 8 to 10 hours, and is used for the short-term treatment of insomnia in people 55 years and older.

Phase III trials have been completed for tasimelteon. LY 156735, beta-methyl-6-chloromelatonin, S-20098 are other melatonin agonists that are currently being studied for effectiveness in treating insomnia.

Non Melatonin Agonists

Lithium. which is used to control bipolar disorder, seems to lengthen the intrinsic period of the pacemaker in the SCN. The antipsychotic haloperidol affects the sleep/wake cycle and could be classified as a chronobiotic. Beta blockers, used to treat hypertension, are known to affect the pineal gland and suppress release of melatonin into the bloodstream.

Alteril™, Melatrol™, Restaid™, and Somulin™ are just a few of the 150 sleep aids available over-the-counter; these preparations contain adequate and safe amounts of natural ingredients that are associated with sleep-promotion. Always check with your doctor before adding a sleep-aid, especially if you have other medical conditions or are taking prescription medications.

Theophylline and pentobarbital are sometimes considered chronobiotics, although these are not often used these days due to side effects. In the past theophylline was used for respiratory diseases, while pentobarbital is an old-style sleeping pill, not mainly used for treatment of seizures. The steroid dexamethasone, often used for arthritis, also has chronobiotic properties.

Photoperiodicity

Photoperiodicity refers to the study of how phyiology and plant and animals respnd to daylight. The word was originally used to refer to a plant's timing of flowering with the length of the day, but has now extended to cover a range of activities and behaviors.