HormonesMelatonin

LMP-melatonin produces greater formulation-dependent effects than conventional melatonin on caffeine-evoked cortical electrical activity and pentobarbital-induced sedative-hypnotic responses in mice

In male BALB/c mice, a lipid-multiparticulate (LMP) melatonin formulation attenuated caffeine-induced increases in cortical spike frequency and altered ECoG amplitude more effectively than conventional melatonin, with strongest effects at 20 mg/kg. LMP-melatonin also reduced latency to and prolonged duration of pentobarbital-induced loss of righting reflex compared to conventional melatonin. However, the study did not assess pharmacokinetic exposure, physiological sleep stages, or neuroprotection.

Last updated: Aug 24, 2026โ€ข0 RCTsโ€ข๐Ÿ“– Read as article โ†’

Evidence Score

Evidence Score24/100
Human RCTโ˜†โ˜†โ˜†โ˜†โ˜†
Meta-analysisโ˜†โ˜†โ˜†โ˜†โ˜†
Mechanismโ˜…โ˜…โ˜…โ˜…โ˜…
Safetyโ˜…โ˜…โ˜…โ˜…โ˜†
Confidencelow

Study Evidence

Study 1. Effects of Melatonin Formulations on Caffeine-Evoked Cortical Activity and Pentobarbital-Induced Sleep in Mice.

observational

Sahin N, Yabas M, Er B, Erten F, Kursun OED, Cikim IG, Kaplan B, Erek G, Ozmen B, Orhan C, Kilic E, Sahin K ยท International journal of molecular sciences (2026)

Participants: N/A
Duration: Acute (single administration)
Intervention: Oral LMP-melatonin (10 or 20 mg/kg) compared to conventional melatonin (10 or 20 mg/kg) in caffeine-treated mice
Outcome: Caffeine-evoked cortical activity (ECoG spike frequency and amplitude), pentobarbital-induced sleep latency and duration, circulating neurochemical and redox markers, neurotransmitter receptor and inflammation-related gene/protein expression
Effect Size: N/A
Population: Eighty-four male BALB/c mice

Result:

PubMed: 42589559DOI: 10.3390/ijms27156906

Mechanism Graph

Caffeine increases cortical spike frequency and alters ECoG amplitude, along with unfavorable changes in neurochemical and redox markers.
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Melatonin formulations attenuate these caffeine-induced changes in a dose-dependent manner.
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LMP-melatonin modulates ECoG activity, biochemical markers, neurotransmitter-receptor expression, and IL-6/TNF-ฮฑ outcomes more than conventional melatonin.
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LMP-melatonin enhances sedative-hypnotic response to pentobarbital (reduced latency, increased duration).

Limitations

  • โš Pharmacokinetic exposure was not assessed, so enhanced bioavailability is not directly established.
  • โš Physiological sleep stages, sleep architecture, and sleep quality were not measured.
  • โš Direct measures of neuronal injury were not evaluated, so neuroprotection cannot be concluded.
  • โš Animal study (mice) with acute pharmacological paradigms, not generalizable to humans.

Frequently Asked Questions

What is LMP-melatonin?โ–ผ

LMP-melatonin is a lipid-multiparticulate formulation of melatonin designed to improve oral delivery, compared to conventional melatonin.

How does LMP-melatonin affect caffeine-induced cortical activity?โ–ผ

In mice, LMP-melatonin at 20 mg/kg attenuated caffeine-induced increases in cortical spike frequency and altered ECoG amplitude more effectively than conventional melatonin.

Does LMP-melatonin improve sleep in this study?โ–ผ

LMP-melatonin enhanced pentobarbital-induced sedative-hypnotic responses (reduced latency to sleep and prolonged sleep duration), but physiological sleep stages were not measured.

Is LMP-melatonin more effective than conventional melatonin?โ–ผ

Yes, in this mouse study, LMP-melatonin showed greater effects on cortical activity, biochemical markers, and sedative-hypnotic responses compared to conventional melatonin.

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References

  1. 1.Sahin N, Yabas M, Er B, Erten F, Kursun OED, Cikim IG, Kaplan B, Erek G, Ozmen B, Orhan C, Kilic E, Sahin K. "Effects of Melatonin Formulations on Caffeine-Evoked Cortical Activity and Pentobarbital-Induced Sleep in Mice.." International journal of molecular sciences, 2026. PMID: 42589559 DOI: 10.3390/ijms27156906
Disclaimer: This content is for educational purposes only and is not medical advice. Evidence scores reflect the quality and quantity of available research, not clinical recommendations. Always consult a healthcare professional before starting any supplement or intervention.