Department of Pharmacy and Pharmacology

stephen_husbands

Head of Medicinal Chemistry

5 West - 3.25

Email: S.M.Husbands@bath.ac.uk

Tel: +44 (0) 1225 383103 

 

Professor Stephen Husbands 

Profile

I use medicinal chemistry to develop a better understanding of the molecular mechanisms underlying neuropsychological diseases, in particular drug abuse, but also including depression and anxiety. To this end, both highly selective ligands and, more recently, ligands targeted at multiple receptors are designed and synthesized, along with specific pharmacological tools such as irreversible and radiolabeled ligands which allow us to study changes in the chemistry of the brain. Manipulation of the duration of activity of ligands has also been a theme within recent years. I am also interested in the therapeutic potential of such compounds, in particular the group is continuing to study, with the help of funding from the National Institute on Drug Abuse, the utility of opioid ligands as treatment agents for opioid, cocaine and other drugs of abuse and the use of opioid ligands in the treatment of depression. The most important work within the group has been towards ‘selectively promiscuous’ ligands and has been driven by the realisation that CNS disorders are rarely simple, requiring complex solutions. Particular success, and impact, has been achieved in delineating the molecular descriptors that are crucial to the unique pharmacological profile displayed by the opioid treatment agent buprenorphine. This work has allowed us to develop ligands that target multiple opioid receptors simultaneously, with some control over efficacy at each receptor. Current targets include the mu, kappa and NOP opioid receptors and, separately, Regulators of G protein Signaling (RGS) proteins. All our work is carried out in collaboration with colleagues at the University of Bath, the University of Michigan, Torrey Pines Institute for Molecular Studies, Imperial College and the University of Bristol. Current and recent funding for our work has come from the National Institute on Drug Abuse, the Medical Research Council and the Cystic Fibrosis Trust.

Publications

Almatroudi, A. M. I., Ostovar, M., Bailey, C., Husbands, S. and Bailey, S., 2017. Forthcoming. Antidepressant-like effects of BU10119, a novel buprenorphine analogue with mixed kappa/mu opioid receptor antagonist properties, in mice. British Journal of Pharmacology

Zielińska, M., Jarmuż, A., Wasilewski, A., Cami-Kobeci, G., Husbands, S. and Fichna, J., 2017. Methyl-orvinol—Dual activity opioid receptor ligand inhibits gastrointestinal transit and alleviates abdominal pain in the mouse models mimicking diarrhea-predominant irritable bowel syndrome. Pharmacological Reports, 69 (2), pp. 350-357.

Grabski, M., Curran, H. V., Nutt, D. J., Husbands, S. M., Freeman, T. P., Fluharty, M. and Munafò, M. R., 2016. Behavioural tasks sensitive to acute abstinence and predictive of smoking cessation success:a systematic review and meta-analysis. Addiction, 111 (12), pp. 2134-2144.

Ding, H., Czoty, P. W., Kiguchi, N., Cami-Kobeci, G., Sukhtankar, D. D., Nader, M. A., Husbands, S. M. and Ko, M.-C., 2016. A novel orvinol analog, BU08028, as a safe opioid analgesic without abuse liability in primates. Proceedings of the National Academy of Sciences of the United States of America

Blazer, L. L., Storaska, A. J., Jutkiewicz, E. M., Turner, E. M., Calcagno, M., Wade, S. M., Wang, Q., Huang, X.-P., Traynor, J. R., Husbands, S. M., Morari, M. and Neubig, R. R., 2015. Selectivity and anti-Parkinson's potential of thiadiazolidinone RGS4 inhibitors. ACS Chemical Neuroscience, 6 (6), pp. 911-919.

Huang, W., Manglik, A., Venkatakrishnan, A. J., Laeremans, T., Feinberg, E. N., Sanborn, A. L., Kato, H. E., Livingston, K. E., Thorsen, T. S., Kling, R. C., Granier, S., Gmeiner, P., Husbands, S. M., Traynor, J. R., Weis, W. I., Steyaert, J., Dror, R. O. and Kobilka, B. K., 2015. Structural insights into μ-opioid receptor activation. Nature, 524 (7565), pp. 315-321.

Husbands, S., 2015. Meet our editorial board member. Mini-Reviews in Medicinal Chemistry, 15 (10), p. 797.

Lowe, J. D., Sanderson, H. S., Cooke, A. E., Ostovar, M., Tsisanova, E., Withey, S. L., Chavkin, C., Husbands, S. M., Kelly, E., Henderson, G. and Bailey, C. P., 2015. Role of G Protein-Coupled Receptor Kinases 2 and 3 in μ-Opioid Receptor Desensitization and Internalization. Molecular Pharmacology, 88 (2), pp. 347-356.

Almatroudi, A., Husbands, S. M., Bailey, C. P. and Bailey, S. J., 2015. Combined administration of buprenorphine and naltrexone produces antidepressant-like effects in mice. Journal of Psychopharmacology, 29 (7), pp. 812-821.

Cueva, J. P., Roche, C., Ostovar, M., Kumar, V., Clark, M. J., Hillhouse, T. M., Lewis, J. W., Traynor, J. R. and Husbands, S. M., 2015. C7β-methyl analogues of the orvinols:the discovery of kappa opioid antagonists with nociceptin/orphanin FQ peptide (NOP) receptor partial agonism and low, or zero, efficacy at Mu opioid receptors. Journal of Medicinal Chemistry, 58 (10), pp. 4242-4249.

Alotaibi, M. R., Husbands, S. M. and Blagbrough, I. S., 2015. 1H, 13C, 15N HMBC, and 19F NMR spectroscopic characterisation of seized flephedrone, cut with benzocaine. Journal of Pharmaceutical and Biomedical Analysis, 107, pp. 535-538.

Khroyan, T. V., Wu, J., Polgar, W. E., Cami-Kobeci, G., Fotaki, N., Husbands, S. M. and Toll, L., 2015. BU08073 a buprenorphine analog with partial agonist activity at μ-receptors in vitro but long-lasting opioid antagonist activity in vivo in mice. British Journal of Pharmacology, 172 (2), pp. 668-680.

Bailey, S., Almatroudi, A. M. I., Bailey, C. and Husbands, S., 2015. The antidepressant-like effects of BU10119, a novel kappa opioid receptor antagonist, in the novelty-induced hypophagia task in mice. In: Society for Neuroscience 2015, 2015-10-17 - 2015-10-21, Chicago.

Bailey, C. P. and Husbands, S. M., 2014. Novel approaches for the treatment of psychostimulant and opioid abuse-focus on opioid receptor-based therapies. Expert Opinion on Drug Discovery, 9 (11), pp. 1333-1344.

Sobczak, M., Cami-Kobeci, G., Sałaga, M., Husbands, S. M. and Fichna, J., 2014. Novel mixed NOP/MOP agonist BU08070 alleviates pain and inhibits gastrointestinal motility in mouse models mimicking diarrhea-predominant irritable bowel syndrome symptoms. European Journal of Pharmacology, 736, pp. 63-69.

Kumar, V., Clark, M.J., Traynor, J.R., Lewis, J.W. and Husbands, S.M., 2014. Pyrrolo- and pyridomorphinans:Non-selective opioid antagonists and delta opioid agonists/mu opioid partial agonists. Bioorganic and Medicinal Chemistry, 22 (15), pp. 4067-4072.

Almatroudi, A., Husbands, S. M., Bailey, C. P. and Bailey, S. J., 2014. Combination Treatment With Buprenorphine/Naltrexone, A Functional Kappa Opioid Receptor Antagonist, Produces Antidepressant-Like Effects In Mice. Journal of Psychopharmacology, 28 (8), A101.

Cordery, S. F., Taverner, A., Ridzwan, I. E., Guy, R. H., Delgado-Charro, M. B., Husbands, S. M. and Bailey, C. P., 2014. A non-rewarding, non-aversive buprenorphine/naltrexone combination attenuates drug-primed reinstatement to cocaine and morphine in rats in a conditioned place preference paradigm. Addiction Biology, 19 (4), pp. 575-586.

Kumar, V., Ridzwan, I.E., Grivas, K., Lewis, J.W., Clark, M.J., Meurice, C., Jimenez-Gomez, C., Pogozheva, I., Mosberg, H., Traynor, J.R. and Husbands, S.M., 2014. Selectively promiscuous opioid ligands:Discovery of high affinity/low efficacy opioid ligands with substantial nociceptin opioid peptide receptor affinity. Journal of Medicinal Chemistry, 57 (10), pp. 4049-4057.

Parker, C.A., Nabulsi, N., Holden, D., Lin, S.-F., Cass, T., Labaree, D., Kealey, S., Gee, A.D., Husbands, S.M., Quelch, D., Carson, R.E., Nutt, D.J., Huang, Y. and Tyacke, R.J., 2014. Evaluation of 11C-BU99008, a PET Ligand for the Imidazoline Binding Sites in Rhesus Brain. The Journal of Nuclear Medicine, 55 (5), pp. 838-844.

Kealey, S., Husbands, S. M., Bennacef, I., Gee, A. D. and Passchier, J., 2014. Palladium-mediated oxidative carbonylation reactions for the synthesis of 11C-radiolabelled ureas. Journal of Labelled Compounds & Radiopharmaceuticals, 57 (4), pp. 202-208.

Casal-Dominguez, J. J., Furkert, D., Ostovar, M., Teintang, L., Clarke, M. J., Traynor, J. R., Husbands, S. M. and Bailey, S. J., 2014. Characterization of BU09059:A novel potent selective κ-receptor antagonist. ACS Chemical Neuroscience, 5 (3), pp. 177-184.

Ju, M., Scott-ward, T. S., Liu, J., Khuituan, P., Li, H., Cai, Z., Husbands, S. M. and Sheppard, D. N., 2014. Loop diuretics are open-channel blockers of the cystic fibrosis transmembrane conductance regulator with distinct kinetics. British Journal of Pharmacology, 171 (1), pp. 265-278.

Bailey, S., Almatroudi, A. M. I., Bailey, C. and Husbands, S., 2014. The antidepressant-like effects of combination buprenorphine/naltrexone in the novelty-induced hypophagia task in mice. In: Society for Neuroscience, 2014-11-15.

Sukhtankar, D. D., Zaveri, N. T., Husbands, S. M. and Ko, M.-C., 2013. Effects of spinally administered bifunctional nociceptin/orphanin FQ peptide receptor/μ-opioid receptor ligands in mouse models of neuropathic and inflammatory pain. Journal of Pharmacology and Experimental Therapeutics, 346 (1), pp. 11-22.

Ko, M.-C. and Husbands, S. M., eds., 2013. Research and Development of Opioid-Related Ligands. American Chemical Society.

Casal-Dominguez, J. J., Clark, M., Traynor, J. R., Husbands, S. M. and Bailey, S. J., 2013. In vivo and in vitro characterization of naltrindole-derived ligands at the κ-opioid receptor. Journal of Psychopharmacology, 27 (2), pp. 192-202.

Kealey, S., Turner, E.M., Husbands, S.M., Salinas, C.A., Jakobsen, S., Tyacke, R.J., Nutt, D.J., Parker, C.A. and Gee, A.D., 2013. Imaging imidazoline-I binding sites in porcine brain using C-BU99008. The Journal of Nuclear Medicine, 54 (1), pp. 139-144.

Husbands, S. M., 2013. Buprenorphine and related orvinols. In: Ko, M.-C. and Husbands, S. M., eds. Research and Development of Opioid-Related Ligands. Washington, DC: American Chemical Society, pp. 127-144.

Almatroudi, A., Husbands, S. M., Bailey, C. P. and Bailey, S. J., 2013. Establishing the combination of buprenorphine and naltrexone as a functional kappa opioid receptor antagonist in mice. Proceedings of the British Pharmacological Society

Greedy, B. M., Bradbury, F., Thomas, M. P., Grivas, K., Cami-Kobeci, G., Archambeau, A., Bosse, K., Clark, M. J., Aceto, M., Lewis, J. W., Traynor, J. R. and Husbands, S. M., 2013. Orvinols with mixed kappa/mu opioid receptor agonist activity. Journal of Medicinal Chemistry, 56 (8), pp. 3207-3216.

Toll, L., Khroyan, T. V., Polgar, W. E., Husbands, S. M. and Zaveri, N. T., 2013. Pharmacology of mixed NOP/mu ligands. In: Ko, M.-C. and Husbands, S. M., eds. Research and Development of Opioid-Related Ligands. Washington, DC: American Chemical Society, pp. 369-391.

Tyacke, R. J., Fisher, A., Robinson, E. S., Grundt, P., Turner, E. M., Husbands, S. M., Hudson, A. L., Parker, C. A. and Nutt, D. 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 imidazoline 2 binding site. Synapse, 66 (6), pp. 542-551.

Turner, E. M., Blazer, L. L., Neubig, R. R. and Husbands, S. M., 2012. Small molecule inhibitors of regulators of G protein signaling (RGS) proteins. ACS Medicinal Chemistry Letters, 3 (2), pp. 146-150.

Bailey, S., Casal-Dominguez, J. and Husbands, S. M., 2012. Antidepressant effects of novel kappa-opioid receptor antagonists in the forced swim test. Journal of Psychopharmacology, 26 (8), A16.

Cami-Kobeci, G., Polgar, W. E., Khroyan, T. V., Toll, L. and Husbands, S. M., 2011. Structural determinants of opioid and NOP receptor activity in derivatives of buprenorphine. Journal of Medicinal Chemistry, 54 (19), pp. 6531-6537.

Kealey, S., Gee, A. D., Husbands, S. M., Bennacef, I. and Passchier, J., 2011. (11)C Urea synthesis via palladium(II)-mediated oxidative carbonylation of amines. Journal of Labelled Compounds & Radiopharmaceuticals, 54 (Supplement 1), S108.

Long, N., Kealey, S., Jennings, L., Miller, P., Gee, A., Plisson, C., White, A. and Husbands, S. M., 2011. Copper(I) tris(pyrazolyl)borate complexes for use in positron emission tomography. Journal of Labelled Compounds & Radiopharmaceuticals, 54 (Supplement 1), S98.

Kealey, S., Plisson, C., Collier, T. L., Long, N. J., Husbands, S. M. and Gee, A. D., 2011. Solution (11)C carbonylation chemistry for the synthesis of a PET tracer - (11)C MK0233. Journal of Labelled Compounds & Radiopharmaceuticals, 54 (Supplement 1), S107.

Kealey, S., Husbands, S. M., Casey, E., Salinas, C. A., Parker, C. A., Jakobsen, S., Tyacke, R. J., Nutt, D. J. and Gee, A. D., 2011. Synthesis and in vivo evaluation of (11)C BU99008 as a ligand for the imidazoline I(2) binding site. Journal of Labelled Compounds & Radiopharmaceuticals, 54 (Supplement 1), S304.

Kealey, S., Jennings, L. E., Miller, P. W., Gee, A. D., Plisson, C., White, A. J. P., Husbands, S. and Long, N. J., 2011. Copper(I) tris(pyrazolyl)borate complexes for use in positron emission tomograhpy. Journal of Labelled Compounds & Radiopharmaceuticals, 54 (7), p. 392.

Blazer, L. L., Zhang, H. M., Casey, E. M., Husbands, S. M. and Neubig, R. R., 2011. A nanomolar-potency small molecule inhibitor of regulator of G-protein signaling proteins. Biochemistry, 50 (15), pp. 3181-3192.

Khroyan, T. V., Polgar, W. E., Cami-Kobeci, G., Husbands, S. M., Zaveri, N. T. and Toll, L., 2011. The first universal opioid ligand, (2S)-2- (5R,6R,7R,14S)-N-cyclopropylmethyl-4,5-epoxy-6,14-ethano-3-hydro xy-6-methoxymorphinan-7-yl -3,3-dimethylpentan-2-ol (BU08028): Characterization of the in vitro profile and in vivo behavioral effects in mouse models of acute pain and cocaine-induced reward. Journal of Pharmacology and Experimental Therapeutics, 336 (3), pp. 952-961.

Taverner, A., Cordery, S., Husbands, S. M., Guy, R. H., Delgado-Charro, B. M. and Bailey, C. P., 2011. Transdermal delivery of a buprenorphine/naltrexone combination for the treatment of polydrug abuse. Pharmacological Reports, 63 (1), p. 257.

Bailey, S. J., Casal-Dominguez, J. J. and Husbands, S. M., 2011. Anxiolytic effects of novel kappa-opioid receptor antagonists in the elevated plus maze. Journal of Psychopharmacology, 25 (8), A76.

Kealey, S., Plisson, C., Collier, T. L., Long, N. J., Husbands, S. M., Martarello, L. and Gee, A. D., 2011. Microfluidic reactions using C-11 carbon monoxide solutions for the synthesis of a positron emission tomography radiotracer. Organic and Biomolecular Chemistry, 9 (9), pp. 3313-3319.

Cami-Kobeci, G., Polgar, W. E., Khroyan, T. V., Toll, L. and Husbands, S. M., 2011. Universal opioid receptor ligands - buprenorphine and related orvinols. Pharmacological Reports, 63 (1), p. 210.

Pichika, R., Jewett, D. M., Sherman, P. S., Traynor, J. R., Husbands, S. M., Woods, J. H. and Kilbourn, M. R., 2010. Synthesis and in vivo brain distribution of carbon-11-labeled delta-opioid receptor agonists. Nuclear Medicine and Biology, 37 (8), pp. 989-996.

Blazer, L. L., Roman, D. L., Chung, A., Larsen, M. J., Greedy, B. M., Husbands, S. M. and Neubig, R. R., 2010. Reversible, allosteric small-molecule inhibitors of regulator of G protein signaling proteins. Molecular Pharmacology, 78 (3), pp. 524-533.

Bailey, S. J., Casal-Dominguez, J. J., Bradbury, F. A., Traynor, J. R. and Husbands, S. M., 2010. In vivo characterisation of 5'-amino and amidino-alkyl,naltrindole derivatives at the kappa-opioid receptor. Journal of Psychopharmacology, 24 (Supplement 3), A42.

Kealey, S., Husbands, S., Casey, E. M., Salinas, C. A., Parker, C. A., Jakobsen, S., Tyacke, R. J., Nutt, D. J. and Gee, A. D., 2010. Synthesis and in vivo evaluation of 11C BU99008 as a ligand for the imidazoline 12 binding site. NeuroImage, 52 (Supplement 1), S127-S128.

Kimura, A., Tyacke, R. J., Robinson, J. J., Husbands, S. M., Minchin, M. C. W., Nutt, D. J. and Hudson, A. L., 2009. Identification of an imidazoline binding protein: Creatine kinase and an imidazoline-2 binding site. Brain Research, 1279, pp. 21-28.

Moynihan, H., Jales, A. R., Greedy, B. M., Rennison, D., Broadbear, J. H., Purington, L., Traynor, J. R., Woods, J. H., Lewis, J. W. and Husbands, S. M., 2009. 14β-O-cinnamoylnaltrexone and related dihydrocodeinones are mu opioid receptor partial agonists with predominant antagonist activity. Journal of Medicinal Chemistry, 52 (6), pp. 1553-1557.

Nieland, N. P. R., Rennison, D., Broadbear, J. H., Purington, L., Woods, J. H., Traynor, J. R., Lewis, J. W. and Husbands, S. M., 2009. 14β-Arylpropiolylamino-17-cyclopropylmethyl-7,8-dihydronormorphinones and Related Opioids. Further Examples of Pseudoirreversible μ Opioid Receptor Antagonists. Journal of Medicinal Chemistry, 52 (21), pp. 6926-6930.

Ko, M. C. and Husbands, S. M., 2009. Effects of atypical kappa-opioid receptor agonists on intrathecal morphine-induced itch and analgesia in primates. Journal of Pharmacology and Experimental Therapeutics, 328 (1), pp. 193-200.

Cami-Kobeci, G., Neale, A. P., Bradbury, F. A., Purington, L. C., Aceto, M. D., Harris, L. S., Lewis, J. W., Traynor, J. R. and Husbands, S. M., 2009. Mixed κ/μ Opioid Receptor Agonists: The 6β-Naltrexamines. Journal of Medicinal Chemistry, 52 (6), pp. 1546-1552.

Collins, G. T., Truccone, A., Haji-Abdi, F., Newman, A. H., Grundt, P., Rice, K. C., Husbands, S. M., Greedy, B. M., Enguehard-Gueiffier, C., Gueiffier, A., Chen, J., Wang, S., Katz, J. L., Grandy, D. K., Sunahara, R. K. and Woods, J. H., 2009. Proerectile Effects of Dopamine D2-Like Agonists Are Mediated by the D3 Receptor in Rats and Mice. Journal of Pharmacology and Experimental Therapeutics, 329 (1), pp. 210-217.

Koffarnus, M. N., Greedy, B., Husbands, S. M., Grundt, P., Newman, A. H. and Woods, J. H., 2009. The discriminative stimulus effects of dopamine D2-and D3-preferring agonists in rats. Psychopharmacology, 203 (2), pp. 317-327.

Spagnolo, B., Calo, G., Polgar, W. E., Jiang, F., Olsen, C. M., Berzetei-Gurske, I., Khroyan, T. V., Husbands, S. M., Lewis, J. W., Toll, L. and Zaveri, N. T., 2008. Activities of mixed NOP and μ-opioid receptor ligand. British Journal of Pharmacology, 153 (3), pp. 609-619.

This list was generated on Mon Sep 25 12:21:15 2017 IST.

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