Opioid Research Group

 ‘Opioid Research Group’ is devoted to drug development, especially development of potential novel therapeutics for several clinically relevant indications such as pain, immunological disorders, gastrointestinal diseases, mood disorders and addiction.

The research goals of the ‘Opioid Research Group’ include: drug design and synthesis, in vitro and in vivo testing and structure-activity relationships (SAR) of novel compounds. Besides the main work on opioid morphinans, the group has been targeting over the years other drug classes (i.e. noscapine analogues, Dopa and Dopamine analogues, PKC inhibitors, NK1 receptor antagonists, L-Type Ca2+-channel blockers).

More than 1,000 compounds have been synthesized and biologically characterized according to protocols established in our laboratories, especially equipped to perform synthetical medicinal chemistry and drug development. Multidisciplinary and synergistic approaches are merged through national and international collaborations. Innovative and highly efficient methodologies are applied in the research program of the ‘Opioid Research Group’, which allow to characterize new drugs and drug actions at the in vitro and in vivo levels, together with mechanistic studies.


Selected references

H. SCHMIDHAMMER, M. SPETEA: “Chemistry of opioids: Synthesis of 14-alkoxymorphinan derivatives and their pharmacological actions” In Top. Curr. Chem. (H. Nagase, Ed.), Springer-Verlag Berlin Heidelberg, 2011, 299, 63.

M. SPETEA, C. R. BOHOTIN, M. F. ASIM, K. STÜBEGGER, H. SCHMIDHAMMER: “ . In Vitro and in Vivo Profile of the 5-benzyl Analogue of 14-Methoxymetopon, a Novel µ Opioid Analgesic with Reduced Propensity to Alter Motor Function“; Eur. J. Pharm. Sci. 2010, 41, 125.

M. SPETEA, I. BILEVICIUTE-LJUNGAR, Y. GUO, J. SCHÜTZ, P. WINDISCH, H. SCHMIDHAMMER: “Peripherally Mediated Antinociception of the µ-Opioid Receptor Agonist 2-[(4,5α-Epoxy-3-hydroxy-14β-methoxy-17-methylmorphinan-6β-yl)amino]acetic acid (HS-731) after Subcutaneous and Oral Administration in Rats with Carrageenan-induced Hindpaw Inflammation”; J. Pharmacol. Exp. Ther. 2006, 317, 220.

R. LATTANZI, M. SPETEA, F. SCHÜLLNER, S. B. RIEF, R. KRASSNIG, L. NEGRI, H. SCHMIDHAMMER: ”Synthesis and Biological Evaluation of 14-Alkoxymorphinans. 22. Influence of the 14-Alkoxy Group and the Substitution in Position 5 in 14-Alkoxymorphinan-6-ones on in Vitro and in Vivo Activities”; J. Med. Chem. 2005, 48, 3372.

S. FÜRST, P. RIBA, T. FRIEDMANN, J. TÍMAR, M. AL-KHRASANI, I. OBARA, W. MARKUCH, M. SPETEA, J. SCHÜTZ, R. PRZEWLOCKI, B. PRZEWLOCKA, H. SCHMIDHAMMER: “Peripheral versus Central Antinociceptive Actions of 6-Amino Acid Substituted Derivatives of 14-O-Methyloxymorphone in Acute and Inflammatory Pain in the Rat”; J. Pharmacol. Exp. Ther. 2005, 312, 609.

M. SPETEA, F. SCHÜLLNER, R. C. MOISA, I. P. BERZETEI-GURSKE, B. SCHRAML, C. DÖRFLER, M. D. ACETO, L. S. HARRIS, A. COOP, H. SCHMIDHAMMER: ”Synthesis and Biological Evaluation of 14-Alkoxymorphinans. 21. Novel 4-Alkoxy and 14-Phenylpropoxy Derivatives of the µ Opioid Receptor Antagonist Cyprodime”; J. Med. Chem. 2004, 47, 3242.

J. SCHÜTZ, M. SPETEA, M. KOCH, M. ACETO, L. S. HARRIS, A. COOP, H. SCHMIDHAMMER: “Synthesis and Biological Evaluation of 14-Alkoxymorphinans. 20. 14-Phenylpropoxymetopon – an Extremely Powerful Analgesic”; J. Med. Chem. 2003, 46, 4182.

M. SPETEA, F. TOTH, J. SCHÜTZ, F. ÖTVÖS, G. TOTH, S. BENYHE, A. BORSODI, H. SCHMIDHAMMER: ”Binding Characteristics of [3H]14-Methoxymetopon, a High Affinity µ-Opioid Receptor Agonist”; Eur. J. Neurosci. 2003, 18, 290.

M. A. KING, W. SU, C. L. NIELAN, A. H. CHANG, J. SCHÜTZ, H. SCHMIDHAMMER, G. W. PASTERNAK: “14-Methoxymetopon, a very Potent µ-Opioid Receptor-selective Analgesic with an Unusual Pharmacological Profile“; Eur. J. Pharmacol. 2003, 459, 203.

R. LATTANZI, L. NEGRI, E. GIANNINI, H. SCHMIDHAMMER, J. SCHÜTZ, G. IMPROTA: “HS-599: A Novel Long Acting Opioid Analgesic Does Not Induce Place-Preference in Rats“; Br. J. Pharmacol. 2001, 134, 441.

E. GREINER, H. SCHOTTENBERGER, K. WURST, H. SCHMIDHAMMER: “Novel Class of Morphinans with Acrylonitrile Incorporated Substructures as Key Intermediates for Non-Oxygen Bridged Opioid Ligands”; J. Am. Chem. Soc. 2001, 123, 3840.

E. FREYE, H. SCHMIDHAMMER, L. LATASCH: “14-Methoxymetopon, a Potent Opioid, Induces No Respiratory Depression, Less Sedation, and Less Bradycardia than Sufentanil in the Dog”; Anesth. Analg. 2000, 90, 1359.

H. SCHMIDHAMMER: "Opioid Receptor Antagonists"; Übersichtsartikel (Buchbeitrag) in Prog. Med Chem. (G. P. Ellis, D. K.Luscombe, A. W. Oxford, eds.) 1998, 35, 83.

H. SCHMIDHAMMER, H. K. JENNEWEIN, R. KRASSNIG, J. R. TRAYNOR, D. PATEL, K. BELL, G. FROSCHAUER, K. MATTERSBERGER, C. JACHS-EWINGER, P. JURA, G. L. FRASER, V. N. KALININ: "Synthesis and Biological Evaluation of 14-Alkoxymorphinans. 11. 3-Hydroxycyprodime and Analogues: Opioid Antagonist Profile in Comparison to Cyprodime"; J. Med. Chem. 1995, 38, 3071.

H. SCHMIDHAMMER, W. P. BURKARD, L. EGGSTEIN-AEPPLI, C. F. C. SMITH: "Synthesis and Biological Evaluation of 14-Alkoxymorphinans. 2. (-)-N-Cyclopropylmethyl-4,14-dimethoxymorphinan-6-one, a Selective µ Opioid Receptor Antagonist"; Med. Chem. 1989, 32, 418.

H. SCHMIDHAMMER, L. AEPPLI, L. ATWELL, F. FRITSCH, A. E. JACOBSON, M. NEBUCHLA, G. SPERK: "Synthesis and Biological Evaluation of 14-Alkoxymorphinans. 1. Highly Potent Opioid Agonists in the Series of (-)-14-Methoxy-N-methylmorphinan-6-ones"; J. Med. Chem. 1984, 27, 1575.