Journal of pineal research
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Melatonin is a highly effective treatment in different animal models of excitotoxicity or ischemia/reperfusion injury. Due to a lack of patentability, commercial sponsors are not interested in funding clinical evaluations of melatonin. Investigators may initiate small-scale clinical evaluation, and intravenous (i.v.) administration is appropriate in acute stroke patients. ⋯ Gross postmortem examination and histological examination of the brain, kidney, liver and spleen did not reveal any evidence of toxicity. In conclusion, melatonin in propylene glycol markedly elevates plasma levels of melatonin with no serious toxicity. This preparation should be further evaluated in human patients.
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Melatonin had previously been shown to reduce up to four 2,2'-azino-bis-(3-ethylbenzthiazoline-6-sulfonic acid) cation radicals (ABTS*+) via a scavenger cascade ending with N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK). However, when melatonin is added to the reaction system in much lower quantities than ABTS*+, the number of radicals scavenged per melatonin molecule is considerably higher and can attain a value of ten. Under conditions allowing for such a stoichiometry, novel products have been detected which derive from AFMK (1). ⋯ When H2O2 is added to the ABTS*+ reaction mixture in quantities not already leading to substantial reduction of this radical, compound 3 is isolated as the major product, whereas 2a and 2b are virtually absent. The substances formed differ from all previously known oxidation products which derive from melatonin and are, among these, the first 3-indolinones. Moreover, the aliphatic side chain at C2 is reminiscent of other substances which have been synthesized in the search for melatonin receptor ligands.