β-carboline binding to imidazoline receptors

A series of β-carbolines were prepared and their affinities for imidazoline (I1 and I2) sites evaluated. Selected compounds were also examined at α2-adrenoceptors. Some of the β-carbolines were found to bind with high affinity to I2-sites and this affinity was dependent on both the planarity of the molecule and the presence of the aryl ring substituents. Good I1-affinity was observed with two of the compounds but none of the tested compounds bound to α2-adrenoceptors. The hallucinogenic properties of β-carbolines have been linked to activity at 5-HT receptors, in particular 5-HT2, however, it is apparent from this study that many of these compounds display substantially higher affinity for the imidazoline sites. This finding, and those showing modulation of some behavioural effects of morphine by I2-ligands, suggests that imidazoline sites may be interesting new targets in drug abuse research.