Prolactin response in Border-Leicester x merino ewes to administration of melatonin, melatonin analogues, a melatonin metabolite and 6-methoxybenzoxazolinone

The effect of structural modifications of the melatonin molecule on plasma half-life of the analogues and basal prolactin secretion was studied in Border-Leicester x Merino ewes. Halogenation at position 6 and/or unsaturation of the 2,3-double bond of the melatonin molecule slightly lengthened the half-life of the analogues. Melatonin, 6-chloromelatonin, 2,3-dihydromelatonin and 6-chloro-2,3-dihydromelatonin decreased plasma prolactin to 31, 45, 54 and 48% of control levels respectively when administered daily (100 micrograms at 1600 h) for 21 days. The brain metabolite of melatonin, N-acetyl-N'-formyl-5-methoxykynurenamine, and the putative natural melatonin analogue, 6-methoxybenzoxazolinone, failed to affect prolactin levels when administered in a similar manner. These results indicate that certain structural modifications to the melatonin molecule can be tolerated biologically; however, the modifications reported here still did not prevent rapid clearance from the circulation.