3, 4 The results shown in Figure 2 led to the following conclusions: Figure 2. Nighttime plasma concentrations of selleck kinase inhibitor melatonin in 12 young subjects (A: June 1994) and 12 elderly subjects (B: October 1994).
Secretion of melatonin by the pineal gland occurs only during the night. Pharmacokinetic analysis shows that the rate of melatonin secretion by the pineal gland is constant Inhibitors,research,lifescience,medical throughout the whole nocturnal pineal melatonin production, for the same subject. The clock times at. the beginning and end of melatonin secretion from the pineal gland are the same for each subject, whatever the season and night, length. Duration of melatonin pineal secretion is between 7.5 and 8 h. Therefore, melatonin secretion and sleep are contemporaneous. Inhibitors,research,lifescience,medical There is a large interindividual variability in the amount, of melatonin released in plasma by the pineal gland during the night in young and old subjects alike. Hypnotic effect of melatonin and NAT in the CNS Results of previous related studies show that melatonin secretion, and therefore the presence of melatonin
in the central nervous system (CNS), is necessary for the induction and maintenance of nocturnal sleep. However, the presence of melatonin in the CNS is insufficient for the induction and Inhibitors,research,lifescience,medical maintenance of sleep. Indeed, Figure 3 and Table I show results Inhibitors,research,lifescience,medical of observations in chicks in an alternate light (L)-dark (D) program (L/D, 12 h:12 h), in which the light phase lasted from 8.00 am until 8.00 pm. When melatonin was administered intramuscularly (pectoralis major muscle) during the light phase from 2.00 pm to 8.00 pm, the chicks did not. exhibit any signs of a hypnotic effect. The absence of a hypnotic effect during the light phase correlated with the very low level of NAT activity in the pineal glands of chicks measured at the same times. Figure 3. Change in N-acetyltransferase (NAT)
activity in the pineal glands of chicks. A. Intramuscular (pectoralis major muscle) administration of tryptamine at 2 pm (arrow) in chicks in a 7-day alternate Calpain Inhibitors,research,lifescience,medical light-dark program (light 8.00 am to 8.00 pm; dark 8.00 … Table I Intramuscular (pectoralis major muscle) administration of melatonin, diazepam, and placebo in chicks under a 7-day alternate light-dark program (LD) (light 8.00 AM to 8.00 PM; dark 8.00 PM to 8.00 AM) or a permanent light program (LL). At 2 PM, the chicks … In contrast, when chicks were observed in a 7-day permanent light, program (L/L, 12 h:12 h), during which NAT activity level was constantly higher,5 the administration of melatonin induced a significant, hypnotic effect. The duration of sleep (between 4 and 5 h) was much greater than that, observed with diazepam (between 1 and 2 h) when it. was administered intramuscularly at the same dose (1 µM per 100 g body weight, at 2.00 pm).