The purpose of this study was to determine the active conformation of a new class of κ-opioids, the bicyclononanones, using well-known κ-selective agonists such as ketocyclazocine, arylacetamides, several isoquinolines, CI 977 and four stereoisomers of EMD-61753. Comparison of the spatial arrangements, electrostatic, hydrophobic, and hydrogen bonding potentials of all κ-selective agonists led to a model of structure-activity relationships of κ-ligands. The arrangement of the pharmacophoric elements are characterized by an almost parallel orientation of the C=O and N-H bonds in conjunction with one or two aromatic rings. Ketocyclazocine is only able to adopt this parallel orientation when the nitrogen atom is inverted in comparison to the X-ray structure. A chair-boat conformation, a protonation at the N7 nitrogen atom, the keto-group and both aromatic rings of the diazabicyclononanones were found to be essentiell for the pharmacophoric conformation. These assumption, that the keto-group is essentiell for the affinity, could be validated by synthesis and binding studies. The pharmacological properties of all considered bicyclononanone derivatives as well as of the four enantiomers of EMD-61753 can be understood and consistently explained in this way.On the basis of the new pharmacophor model it was possible to develop first suggestions for new κ-ligands with high affinity.