melatonin

6 interactions related to melatonin

propranolol + melatonin

Propranolol blocks pineal beta-1 adrenergic receptors that control endogenous melatonin synthesis, suppressing nighttime melatonin levels by roughly 50% and contributing to insomnia, vivid dreams, and reduced sleep efficiency. Low-dose oral melatonin at bedtime can restore sleep architecture without compromising propranolol's antihypertensive effect.

moderate
propranololmelatoninbeta-blockerinsomniasleepcircadianhypertensionpineal

zolpidem + melatonin

Combining the Z-drug hypnotic zolpidem with melatonin can produce additive next-day drowsiness, impaired thinking, and reduced motor coordination, with the risk most pronounced in older adults. The interaction is primarily pharmacodynamic.

moderate
zolpidemambienmelatoninz-drugsedationsleep aidnext-day impairmentdrowsiness

alprazolam + melatonin

Melatonin and alprazolam both promote sleep and can produce additive sedation, impaired alertness, and reduced motor coordination when used together. The combination may increase next-day drowsiness and risk during activities like driving.

moderate
alprazolamxanaxmelatoninbenzodiazepinesedationsleep aiddrowsinessnext-day impairment

metoprolol + melatonin

Metoprolol blocks the beta-1 adrenergic receptors that drive pineal melatonin synthesis, suppressing endogenous nighttime melatonin and contributing to insomnia, vivid dreams, and reduced sleep efficiency. Low-dose oral melatonin can restore sleep without interfering with metoprolol's cardiovascular benefits.

moderate
metoprololmelatoninbeta-blockerinsomniasleephypertensioncircadianpineal

melatonin + magnesium

Melatonin signals the brain that it is biological night through MT1 and MT2 receptors in the suprachiasmatic nucleus, while magnesium acts as a NMDA antagonist and GABA-A agonist, helping the nervous system actually relax around that signal. A double-blind RCT in nursing home residents with primary insomnia (Rondanelli 2011) found that nightly melatonin 5 mg + magnesium 225 mg + zinc 11.25 mg significantly improved sleep quality, ease of falling asleep, and morning alertness versus placebo.

low
melatoninmagnesiumsleepinsomniacircadiansynergynighttimeelderly

diphenhydramine + melatonin

Both diphenhydramine and melatonin cause sedation through different mechanisms (H1 antagonism and MT1/MT2 agonism). Combined use produces additive CNS depression, next-day drowsiness, impaired cognition, and increased fall risk, especially in older adults.

moderate
diphenhydraminemelatoninbenadrylsedationsleep aidcns depressionbeers criteriainsomnia