Novel Dimethyltyrosine-Tetrahydroisoquinoline Peptidomimetics with Aromatic Tetrahydroisoquinoline Substitutions Show in Vitro Kappa and Mu Opioid Receptor Agonism.

Deanna Montgomery, Jessica P Anand, Nicholas W Griggs, Thomas J Fernandez, Joshua G Hartman, Ashley A Sánchez-Santiago, Irina D Pogozheva, John R Traynor, Henry I Mosberg

ACS chemical neuroscience 2019 Aug 21

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The dimethyltyrosine-tetrahydroisoquinoline (Dmt-Tiq) scaffold was originally developed in the production of selective delta opioid receptor (DOR) antagonists. Installation of a 7-benzyl pendant on the tetrahydroisoquinoline core of this classic opioid scaffold introduced kappa opioid receptor (KOR) agonism. Further modification of this pendant resulted in retention of KOR agonism and the addition of mu opioid receptor (MOR) partial agonism, a bifunctional profile with potential to be used in the treatment of cocaine addiction.

Citation

Deanna Montgomery, Jessica P Anand, Nicholas W Griggs, Thomas J Fernandez, Joshua G Hartman, Ashley A Sánchez-Santiago, Irina D Pogozheva, John R Traynor, Henry I Mosberg. Novel Dimethyltyrosine-Tetrahydroisoquinoline Peptidomimetics with Aromatic Tetrahydroisoquinoline Substitutions Show in Vitro Kappa and Mu Opioid Receptor Agonism. ACS chemical neuroscience. 2019 Aug 21;10(8):3682-3689