Future therapies for diseases associated with altered dopaminergic signaling, including Parkinson\u2019s disease, schizophrenia and drug addiction or drug dependence, may be substantially built on the existence of intramembrane receptor-receptor interactions within receptor mosaics where it is believed that the D2
receptor may operate as the \u201chub receptor\u201d [1]. In particular, it has been proposed that striatal dopaminergic neurotransmission could be under the control of receptor heteromers containing D2 autoreceptors and non-alpha7 nicotinic acetylcholine
heteroreceptors [2]. In an attempt to investigate the biochemical and functional interactions
between dopaminergic autoreceptors and nAChRs containing the beta2 subunit, we
designed and prepared a group of potential bifunctional derivatives incorporating a D2/D3 agonist moiety and a nicotinic alpha4beta2 antagonist fragment, linked by polymethylene spacers of different length. The new compounds have been biologically characterized for their affinity/specificity/functional profile at the target nACh and D2 receptor subtypes. The synthesis of the designed derivatives and the results of their pharmacological investigation will be presented and discussed. [1] K.Fuxe, D.Marcellino, A.Rivera, Z.Diaz-Cabiale, M.Filip, B.Gago, D.C.S.Roberts,
U.Langel, S.Genedani, L.Ferraro, A.de la Calle, J.Narvaez, S.Tanganelli,
A.Woods, L.F.Agnati, Brain Res.Rev., 58, 2008, 415-452. [2] D.Quarta, F.Ciruela, K.Patkar, J.Borycz, M.Solinas, C.Lluis, R.Franco, R.A.Wise,
S.R.Goldberg, B.T.Hope, A.Woods, S.Ferr\ue9, Neuropsychopharmacol., 32, 2007, 35-42
