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Methods for treating circadian rhythm phase disturbances
| Details |
Inventors: Lewy, Alfred J.; Sack, Robert L.;
Assignee: State of Oregan, Acting by and Through the Oregon State Board of Higher (Portland, OR)
Primary Examiner: O'Sullivan; Peter
Assistant Examiner:
Attorney, Agent or Firm: Banner & Allegretti, Ltd.
A method for treating circadian rhythm phase disorders is described. The invention provides methods to specifically advance or delay the phase of certain circadian rhythms in humans. The disclosed methods relate to the administration of melatonin at times determined with relation to the time of dim light endogenous melatonin onset. Embodiments capable of alleviating the effects of jet lag, winter depression and shift-work sleep disturbance are provided. |
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DETAILED DESCRIPTION This invention relates to methods for achieving a chronobiologic (phase-shifting) effect in a human.
This effect is achieved by affecting a human's circadian rhythm by administering exogenous melatonin to the human at an appropriate time relative to the human's dim light endogenous melatonin onset time.
The circadian rhythm of melatonin production in a human is entrained principally by the (bright) light-dark cycle and reflects a variety of other biological properties which vary with a circadian rhythm.
The methods of the invention entail the phase-shifting of circadian rhythms by administration of exogenous melatonin.
More specifically, the method of the invention involves the administration of a particular dosage of melatonin to the human.
The present invention contemplates the administration of various doses of melatonin which promote quantitative shifts in an individual's endogenous circadian pacemaker.
The administration of sufficient doses of melatonin is capable of shifting the pacemaker, as well as the melatonin PRC, by an appropriate degree.
A linear dose effect has been found as described hereinbelow at melatonin dosages from about 0.
125 mg to about 0.
5 mg melatonin.
Thus, in a preferred embodiment, melatonin is administered in dosages preferably from about 0.
05 to 5 mg, more preferably from about 0.
1 to 2 mg, and most preferably from about 0.
1 to 1 mg.
In a preferred embodiment, the total dose of melatonin is given in one dose.
The present invention also contemplates the use of melatonin precursors, agonists, antagonists, and compounds which mimic melatonin activity, in place of melatonin (N-acetyl-5-hydroxytryptamine) itself.
Further, the method of the invention relates to the timing of the administration of the dosage of melatonin to the human.
The timing of this dosage in the human as described results in a specific phase shift in the human's circadian rhythm of endogenous melatonin production.
The method described in the invention can be used to advance or delay the phase of the circadian rhythm of melatonin production in the human
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