Identification of the adenine binding site of the human A(1) adenosine receptor

Medicinal Chemistr

Antigonadal effects of two novel melatonin analogues in adult Djungarian hamsters

This study examined the effects of two novel melatonin analogues in adult Djungarian hamsters housed under long photoperiod (LD 16:8). Daily injection (10 μg, s.c.) of either melatonin, 5-methoxy N-butanoyltryptamine (bMT), or 5-methyl N-butanoyltryptamine (5-MebT) 3 hr before lights off for 8 weeks led to a significant decrease in paired testis weight compared to vehicle-injected controls. The reduction in testis weight was of similar magnitude with melatonin and bMT, but 5-MebT was not as effective. The affinity of the analogues was determined in competition experiments using chicken brain membranes and 2-[125I]iodomelatonin (2-[125I]aMT). Replacing the N-acetyl side-chain of melatonin with an N-butanoyl group increased affinity for the chicken brain 2-[125I]aMT binding site, but exchanging the 5-methoxy group of melatonin for a 5-methyl group reduced affinity. These studies show that these analogues not only inhibit 2-[125I]aMT binding in vitro but also mimic melatonin's antigonadal activity in vivo