Dosage of promethazine for sleep. No effect on respiratory rate and tidal volume. In healthy volunteers, administration of promethazine in doses 60 mg twice every 4 hours for 3 consecutive nights significantly reduced daytime sleepiness but not sleep latency (12). In contrast, p-glycoprotein decreased during the night and also in morning. An increase serum concentrations of cortisol, which is associated with an increase in Promethazine 25mg $44.64 - $0.74 Per pill sleep latency, was seen during the night. These findings were corroborated by the that increase in number of awakenings and the sleep latency was significantly decreased by administration of promethazine (14). Sleep onset latency in healthy volunteers was reduced by promethazine (5 mg/kg orally) and did not improve by administration of caffeine (10 mg/kg) (15). Although increased sleep latency, the effects were less than those of promethazine. In a normal sleep-wake cycle, caffeine prevents sleep onset by decreasing cortisol secretion from peripheral tissues into the bloodstream (16). It also blocks the effects of sympathomimetic amines, norepinephrine and serotonin, which act on the central nervous system to facilitate sleep (17). Promethazine can, however, stimulate sympathetic and parasympathetic stimulation during light sleep (18). by caffeine during could lead to increased serotonin and norepinephrine, which in turn would decrease sleep latency (20, 21). A recent study showed that promethazine (10 mg/kg) reduced the sleep times of rats and reduced the size of sleep stage (22). The present study tested whether promethazine would delay sleep when given 30 minutes before sleep onset. No effects of promethazine on sleep were seen at 30 minutes before onset or when promethazine was given 30 or 60 minutes before sleep onset. As shown in, sleep latency was slowed in a dose-dependent fashion and did not show significant difference for the three doses of promethazine. These changes were not seen in the untreated rats nor among treated with caffeine. In fact, there was a clear dose-response relation for sleep latency. The increase in latency was significant up to three times higher doses of promethazine than for caffeine. The maximum effect on sleep latency is only achieved when both a) administration of promethazine and caffeine b) administration of these drugs at the same time. At 120 minutes after the administration of caffeine (10 mg/kg orally), the sleep latency of sleep-disordered rats was reduced by about 15 minutes. A sleep-disordered state that is associated with a tendency to fall asleep during the daytime is characteristic of caffeine-treated rats (23). In healthy rats, administration of caffeine at 60 minutes before start of sleep delayed duration only when promethazine or caffeine were simultaneously administered (24). Administration of caffeine alone to normal sleep-disordered rats, however, had no significant effect on sleep duration. Promethazine showed no influence on the sleep stage in sleep-disordered rats. This finding might lead to the conclusion that promethazine has no effect on sleep in all disorders when given before sleep onset or at the times when sleep onset is delayed. It is well established that the release of norepinephrine increases to a considerable extent when there is an electrical stimulation of the dorsal raphe nucleus. Caffeine, on the other hand, blocks this stimulation and norepinephrine release from the dorsal raphe nucleus as demonstrated by a potentiation of acetylcholine-evoked firing hippocampal CA1 neurons ()
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