No indications for CYP-inducing effects in therapeutic use. Possibly promoting formation of anti-porphyrogenic GABA , otherwise no conceivable effects on hepatic nuclear PXR/CAR-activation. Safely used in one 24 y PBGD deficient female.

N-[2-(5-Methoxyindol-3-yl)ethyl]acetamide. M= 232.3. Hormone structurally related to tryptofan, (acetylmethoxytryptamine).

Melatonin is used in short duration monotherapy of primary age-related insomnia characterized by impaired quality of sleep in elderly > 55 y. It enhances the activity of pyridoxal kinase, an enzyme involved in the synthesis of aminobutyric acid, dopamine and serotonin. Its activity on the MT1- MT2- and MT3-receptors engaged in circadian regulation probably explains the variation of melantoin secretion with the light-darkness cycle. Physiologically the secretion rises shortly after dark reaching a maximum between 02 and 04 in the morning and decreasing during the rest of the night.

Significant.

After peroral administration it is readily absorbed with a first pass metabolism of 85 per cent. The cytochrome P450 1A1 is the main effector of the metabolism. CYP 1A2, CYP 2D and possibly CYP 2C19 also take part in the hepatic biotranformation to the inactive metabolite 6-sulphatoxymelatonin (6-S-MT). Cmax is 3-4 times higher in women compared to men, but there is also a five-fold interindividual variation between persons of the same gender. In supra -therapeutic concentrations observed in vitro to induce CYP 3A4. The clinical relevance of this induction is not known. It is probably insignificant in therapeutic use of the drug in the absence of co-administered drugs giving rise to inhibition of its biotransformation. There are no observations of CYP-inducing effects in clinical use. Co-administration of drugs, including estrogens in contraception or in hormon replacement therapy, with capacity to inhibit CYPs 1A1, 1A2 and 2D give rise to increased exposure to melatonin. There may be inhibitory effect on nuclear PXR activation via its promotion of GABA synthesis (1).

Used according to recommendation with good effect against insomnia by a female 24 y old patient who is a carrier of PBGD deficiency (STh sept 09).

Uneventful use reported in 4 patients with acute porphyria.