Studies have shown that compounds with piperidine ring have selectivity for NK1 receptor over NK2, NK3, opioid and 5-HT receptors. By adding an N-heteroaryl-2-phenyl-3-(benzyloxy) group to the piperidine, a selective NK1 receptor antagonist is produced. Studies have also shown that the dihedral angle between groups on C-2 and C-3 in CP-99994 is critical for activity of the NK1 receptor antagonists. The bridgehead basic nitrogen is thought to interact with the NK1 receptor by mediating its recognition through ion pair site. It has been found that the basic nitrogen atoms in pyrido[3,4-b]pyridine do have an anchoring function in the phospholipid component of the cell membrane.