Oleamide: A Fatty Acid Amide with Sleep-Inducing and Analgesic Effects

Oleamide is a long-chain fatty acid amide lipid messenger discovered in human serum in 1989. It accumulates in the cerebrospinal fluid of sleep-deprived cats and has been shown to regulate sleep, body temperature, and act as an analgesic in pain models. While its pharmacological effects are evident, the biochemical pathway for oleamide synthesis remains uncertain.

Key findings from research on oleamide include:

• Administration to rats reduces motor activity and increases oleamide levels in the cerebrospinal fluid following sleep deprivation.
• Oleamide reduces sleep latency without affecting other sleep parameters and induces changes in brain electrical activity.
• It enhances serotonergic and GABAergic neurotransmission, pathways involved in sleep induction.
• Oleamide could represent a new class of biological signaling molecules in sleep regulation.

The synthesis of oleamide may proceed via the enzyme peptidylglycine alpha-amidating monooxygenase (PAM), or through the direct amidation of oleic acid. Oleamide interacts with various receptors and channels, including GABA(A), 5-HT(7), and cannabinoid receptors. Notably, oleamide is a potent vasodilator in rat small mesenteric arteries, acting through a mechanism independent of conventional cannabinoid receptors.

Oleamide's selective action on glial cell gap junctions suggests a role in controlling brain cell communication, potentially influencing sleep induction. It modulates 5-HT2 receptors, indicating a new mechanism for regulating receptors that activate G proteins.

Structural features necessary for oleamide to inhibit gap junction communication include a specific carbon chain length, a polar terminal carbonyl group, a cis double bond, and a hydrophobic methyl end. Oleamide's enzymatic production within rat brain tissue has been confirmed, and it is broken down by fatty acid amide hydrolase (FAAH).

Oleamide's role in the heart and circulation is yet to be fully understood, but the range of actions attributed to it suggests it could significantly modulate cardiovascular function. It may also act as a signaling molecule within the cardiovascular system.

Considerations for Future Studies

Future research should focus on clarifying oleamide's physiological role, its production within the cardiovascular system, and the potential for therapeutic applications.

References:

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