RS-30199 has been shown previously to have atypical interactions at 5-HT 1 A receptors. RS-30199 and RS-64459, an analogue of buspirone with a buspirone side chain, were compared with the classic, partial agonist at 5-HT 1 A receptors, 8-hydroxy-2 (di-n-propylamino) tetralin (8-OH-DPAT) and buspirone. At human (h) 5-HT 1 A receptors in CHO cells, RS-30199-193 (racemate) and its enantiomers (-197, -198) inhibited [ 3 H]-8-OH-DPAT binding (RS-30199-198, k i , 29.7±11.7 nM; RS-30199-197, k i , 74.1±11.7 nM) as did RS-64459 (k i , 24.9±6.0 nM), but RS-30199-197 and -198 were almost full agonists in a [ 3 5 S]-GTPγS binding assay, whereas RS-64459 was a partial agonist, resembling buspirone and 8-OH-DPAT. RS-64459 and the enantiomers of RS-30199 had weaker affinity for 5-HT 2 C and 5-HT 7 receptors. These compounds did not induce the 5-HT behavioural syndrome in male rats. However, in a model where naive male rats were introduced to estrogen-progesterone primed, sexually receptive female rats, RS-30199-197 (0.1, 1, 10 mg/kg, s.c.) had a profound inhibitory effect on sexual behaviour score. Neither buspirone nor 8-OH-DPAT reduced the sexual behaviour score. Unlike 8-OH-DPAT, which shortens intromission latency, RS-30199 prolonged intromission latency. RS-30199 (10 mg/kg s.c.) fully inhibited the facilitation of sexual behaviour caused by the α 2 -adrenoceptor antagonist, delequamine (0.1 mg/kg, p.o.). In contrast, RS-64459 (100, 250, 1000 and 4000 μg/kg, s.c.) failed to modify the sexual behaviour score and did not modify intromission latency. The differences between the effects of RS-30199 and RS-64459 in binding and functional experiments are supported by molecular models of the receptor-ligand interaction, where the compounds interact in different ways with the receptor; a model is proposed for the allosteric interaction of different agents with the receptor, resulting in different functional profiles. RS-30199 can be considered an atypical agonist at 5-HT 1 A receptors.