The selective potentiation and/or inhibition of the 5-HT.sub.2A and/or
5-HT.sub.1A response to serotonin (5-HT) is achieved using analogs of
oleamide. Selective potentiation and/or inhibition of the 5-HT.sub.2A
and/or 5-HT.sub.1A leads to a modulation of serotonergic signal
transduction of cells having various receptor subtypes. A subset of
analogs is identified that inhibits rather than potentiates the
5-HT.sub.2A, but not the 5-HT.sub.1A, receptor response. These analogs
enable the selective modulation of serotonin receptor subtypes and even
have opposing effects on the different subtypes. An analysis of the
activity of the oleamide analogs discloses that the structural features
required for activity are highly selective. In particular, the presence,
position, and stereochemistry of the 9-cis double bond is required and
even subtle structural variations reduce or eliminate activity. Secondary
or tertiary amides may replace the primary amide but follow a well-defined
relationship requiring small amide substituents suggesting that the
carboxamide serves as a hydrogen bond acceptor but not donor. Alternative
modifications at the carboxamide as well as modifications of the methyl
terminus or the hydrocarbon region spanning the carboxamide and double
bond typically eliminate activity.
