Current Research

Insect Olfactory Receptors · Mammalian Olfactory Receptors · Neuronal Nicotinic Receptors
 
Neuronal Nicotinic Receptors
 
Neuronal nAChRs are of interest for several reasons.  Nicotinic ligands are potentially useful as anxiolytics and analgesics, and in the treatment of neurological disorders such as schizophrenia, Parkinson's disease, and Alzheimer's disease.  Neuronal nAChRs are also the sites at which nicotine exerts its psychoactive and addictive effects.  Thus, pharmacological intervention at neuronal nAChRs holds promise for treating the effects of diseases of the central nervous system and for understanding and treating addictive processes.  Critical to the realization of this potential is the development of selective nAChR ligands.  We are currently collaborating with Ivy Carroll's group (Research Triangle Institute) to examine the functional effects of modifications to the structure of epibatidine (an exceptionally potent nicotinic agonist).
    
Recent Publications
  
Ondachi, P., Castro, A.H., Sherman, B., Luetje, C.W., Wageman, C.R., Marks, M.J., Damaj, M.I., Mascarella, W.W., Navarro, H.A., Carroll, F.I. (2017) Synthesis, nicotinic acetylcholine receptor binding, in vitro and in vivo pharmacological properties of 2’-fluoro-(substituted thiophenyl)deschloroepibatidine analogs.  ACS Chemical Neuroscience 8: 115-127.  
  
Ondachi, P., Castro, A.H., Luetje, C.W., Wageman, C.R., Marks, M.J., Damaj, M.I., Mascarella, W.W., Navarro, H.A., Carroll, F.I. (2016) Synthesis, nicotinic acetylcholine binding, in vitro and in vivo pharmacological properties of 2’-fluoro-(carbamoylpyridinyl)deschloroepibatidine analogs.  ACS Chemical Neuroscience 7: 1004-1012.    
  
Ondachi, P., Ye, Z., Castro, A.H., Luetje, C.W., Damaj, M.I., Mascarella, W.W., Navarro, H.A., Carroll, F.I. (2015) Synthesis, nicotinic acetylcholine receptor binding, in vitro and in vivo pharmacology properties of 3'-(substituted pyridinyl)-deschloroepibatidine analogues.  Bioorganic & Medicinal Chemistry 23: 5693-5701
   
Carroll, F.I., Navarro, H.A., Mascarella, S.W., Castro, A.H., Luetje, C.W., Wageman, C.R., Marks, M.J., Jackson, A., Damaj, M.I. (2015) In vitro and in vivo neuronal nicotinic receptor properties of (+)- and (-)- pyrido[3,4] homotropane [(+)- and (-)-PHT]. (+)-PHT is a potent and selective full agonist at α6β2 containing neuronal nicotinic acetylcholine receptorsACS Chemical Neuroscience 6: 920-926. 
   
Ondachi, P., Castro, A.H., Bartkowiak, J.M., Luetje, C.W., Damaj, M.I., Mascarella, W.W., Navarro, H.A., Carroll, F.I. (2014) Synthesis, Nicotinic Acetylcholine Receptor Binding and Antinociceptive Properties of 2'-Fluoro-3'-(Substituted pyridinyl)-7-deschloroepibatidine Analogues.  Journal of Medicinal Chemistry 57: 836-848.  
    
 
Franco, A., Kompella, S.N., Akondi, K., Melaun, C., Daly, N., Luetje, C.W., Alewood, P.F., Craik, D.J., Adams, D.J., Mari, F. (2011) RegIIA: An α4/7-conotoxin from the venom of Conus regius that potently blocks a3b4 nAChRs.  Biochemical Pharmacology 83:419-426.  
  
Hsiao, B., Mihalak, K.B., Magleby, K.L., Luetje, C.W. (2008) Zinc potentiates neuronal nicotinic receptors by increasing burst duration.  Journal of Neurophysiology 99:999-1007.
  
Mihalak, K.B., Carroll, F.I., Luetje, C.W. (2006) Varenicline is a partial agonist at alpha4beta2 and a full agonist at alpha7 neuronal nicotinic receptors.  Molecular Pharmacology 70:801-805.
   
Hsiao, B., Mihalak, K.B., Repicky, S.E., Everhart, D., Mederos, A., Malhotra, A., Luetje, C.W. (2006) Determinants of zinc potentiation on the alpha4 subunit of neuronal nicotinic receptors.  Molecular Pharmacology 69:27-36.