Oleamide-mediated sleep induction does not depend on perturbation of membrane homeoviscosity.
To verify whether the sleep-inducing properties of oleamide were related to its ability to perturb membrane homeoviscosity, affecting 5-HT(2A) receptors, we compared the effects of oleamide and oleic acid, the latter lacking both the sleep-inducing effect and the action on 5-HT(2A) receptors. In binding studies the two compounds did not directly interact with rat brain cortex 5-HT(2A) receptors, nor did they increase the affinity of a 5-HT(2A) agonist, either in vitro or ex vivo. They had similar fluidizing effects, in vitro at high concentrations (>/=10 microM), and ex vivo after a dose of 100 mg/kg, and they reduced locomotor activity with similar potency. There thus appears to be no causal relationship between the fluidizing effects of oleamide and its sleep-inducing properties.
Gobbi
M
M
Department of Molecular Biochemistry, Istituto di Ricerche Farmacologiche 'Mario Negri', Via Eritrea 62, 20157, Milan, Italy. gobbi@irfm.mnegri.it
Mennini
T
T
Valle
F D
FD
Cervo
L
L
Salmona
M
M
Diomede
L
L
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D005454:Fluorescence Polarization; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D008297:Male; D008560:Membrane Fluidity / Q000187:drug effects; D019301:Oleic Acid / Q000494:pharmacology; D009829:Oleic Acids / Q000494:pharmacology*; D051381:Rats; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D012890:Sleep / Q000187:drug effects*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D006993:Hypnotics and Sedatives; D009829:Oleic Acids; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D019301:Oleic Acid; C029407:oleylamide