My current research covers two main areas of interest:Firstly, the effects of ecstasy on brain neurochemistry and rodent behaviour, and second, the structure, function and pharmacology of alpha-2-adrenoceptors and imidazoline receptors.
Ecstasy abuse is of prime interest at present as Canada is a leading manufacturer and exporter of the component substances found in ecstasy tablets. Recent tragic deaths following the ingestion of the drug ecstasy have highlighted how widespread the use of this drug and so called "legal highs" are in Canada. Ecstasy ((±)-3-4-methylenedioxy-methamphetamine, MDMA) tablets are usually not pure but also contain related piperazine derivatives (benzylpiperazine. BZP, 3-trifluoromethyl-phenylpiperazine, TFMPP, 1-(3-chlorphenyl)-piperazine, mCPP), with some tablets containing BZP alone.We are using a rodent model to investigate the neurochemical and behavioural effects of these substances to determine their effects on monoamine turnover using brain microdialysis. We are also looking at drugs that have the potential to block the effects of ecstasy with a view to their clinical use to treat acute ecstasy overdose.
Alpha-2-adrenoceptors and imidazoline receptors are of great interest to us as they also regulate the turnover of monoamines in the brain. In mammalian systems modulation of central monoamine levels can have a profound effect on mood, anxiety, cognition. Much of my work uses new and novel synthetic ligands combined with a variety of in vitro and in vivo techniques to improve our understanding of the role of these receptors in normal and diseased brain. A greater understanding of these receptors may lead to improved therapies for mood disorders including depression and drug addiction.
Silverstone, PH., Lalies, MD., Hudson, AL. (2012) Quetiapine and buspirone both elevate cortical levels of noradrenaline and dopamine in vivo, but do not have synergistic effects. Frontiers of Psychiatry, 3, 1 - 5.
Hudson, AL., Lalies, MD., Silberstone, P. (2012) Venlafaxine enhances the effect of bupropion on extracellular dopamine in rat frontal cortex. Can. J. Physiol. Pharmacol. 90, 803-809.
Tyacke, Robin J., Parker, Christine A., Robinson, Emma SJ., Turner, Emma M., Fisher, Amy, Grundt, Peter, Hudson, Alan L., Husbands, Stephen M., Nutt, David J. (2012) Evaluation and initial in vitro and ex vivo characterization of the potential positron emission tomography ligand, BU99008 (2-(4,5-dihydro-1H-imidazol-2-yl)-1-methyl-1H-indole), for the imidazoline2 binding site. Synapse, 66, 542-51.
Mammoli, Valerio, Bonifazi, Alessandro, Del Bello, Fabio, Diamanti, Eleonora, Giannella, Mario, Hudson, Alan L., Mattioli, Laura, Perfumi, Marina, Piergentili, Alessandro, Quaglia, Wilma, Titomanlio, Federica, Pigini, Maria. (2012) Favourable involvement of a 2A-adrenoreceptor antagonism in the 12 imidazoline binding sites-mediated mrophine analgesia enhancement. Bioorg & Med Chem. 20, 2259-2265.
Jaroslaw Saczewski, Alan Hudson, Mika Scheinin, Apolonia Rybczynska, Daqing Ma, Franciszek Saczewski, Shayna Laird, Jonne M. Laurila, Konrad Boblewski, Artur Lehmann, Jianteng Gu, Helena Watts. (2012) Synthesis and biological activities of 2-[(heteroaryl)methyl]imidazolines. Bioorg & Med Chem., 20, 108-116.
Jaroslaw Saczewski, Alan Hudson, Shayna Laird, Apolonia Rybczynska, Konrad Boblewski, Artur Lehmann, Daqing Ma, Mervyn Maze, Helena Watts, and Maria Gdaniec. (2012) N-(Imidazolidin-2-ylidene)-1-arylmethanamine Oxides: Synthesis, Structure and Pharmacological Evaluation. Arch. Pharm. Chem. Life Sci., 345, 33-42.
Treder, A., Andruszkiewicz, R., Zgoda, W., Ford, C & Hudson, A. (2011) New imidazoline/α2-adrenoceptors affecting compounds—4(5)-(2-aminoethyl)imidazoline (dihydrohistamine) derivatives. Synthesis and receptor affinity studies. Bioorg & Med Chem., 19., 156-167. PMID: 21159515.
Franciszek Sączewski, Anita Kornicka, Alan L. Hudson, Shayna Laird, Mika Scheinin, Jonne M. Laurila, Apolonia Rybczyńska, Konrad Boblewski, Artur Lehmann, Maria Gdaniec (2011). 3-[(Imidazolidin-2-yl)imino]indazole ligands with selectivity for the α2-adrenoceptor compared to the imidazoline I1 receptor. Bioorg & Med Chem., 19, 321-329. PMID: 21129985.
Giorgioni, G., Ambrosini, D., Vesprini, C., Hudson, A., Nasuti, C., Stafeano, A., Sozio, P., Ciampi, O., Costa, B., Martini, C., Carrieri, A., Carbobara, G., Enzensperger, C. & Pigini, M. (2010) Novel imidazoline compounds as partial or full agonists of D2-like dopamine receptors inspired by I2-imidazoline binding sites ligand 2-BFI. Bioorg & Med Chem., 18, 7085-7091.
Kimura, A., Tyacke, R., Robinson, J., Husbands, S., Minchin, M., Nutt, A.J. & Hudson, A.L. (2009) Identification of an imidazoline binding protein: Creatine kinase and an imidazoline-2 binding protein. Brain Research., 1279, 21-28. PMID: 19410564
Treder, A., Andruszkiewicz, R., Zgoda, W., Ford, C & Hudson, A. (2009) New analogues of agmatine with higher affinity to imidazoline receptors. Bioorg & Med Chem Letters., 19, 1009-1011. PMID: 19101144.
Abu Ghazaleh, H., Lalies, M.D, Husbands, S.M, Nutt, D.J. & Hudson, A.L. (2007) The effect of 1-(4,5-dihydro-1H-imidazol-2-yl) isoquinoline on monoamine release and turnover in the rat frontal cortex. Neuroscience Letters, 422, 109-113. PMID: 17602837.