title: mGlu1 receptor as a drug target for treatment of substance use disorders: time to gather stones together?
abstract: Modulation of the mGlu1 receptor was repeatedly shown to inhibit various phenomena associated with exposure to abused drugs. Efficacy in preclinical models was observed with both positive and negative allosteric modulators (PAMs and NAMs, respectively) using essentially non-overlapping sets of experimental methods. Taken together, these data indicate that the mGlu1 receptor certainly plays a significant role in the plasticity triggered by the exposure to abused drugs and is involved in the maintenance of drug-seeking and drug-taking behaviors. Understanding whether modulation of the mGlu1 receptor activity can also affect drug-seeking and drug-taking in humans could have a significant impact on the future development of medications in this field. We argue that the mGlu1 receptor NAMs have a significant value as potential tools for human experimental pharmacology that could help to validate methods used in preclinical research. Compared with the PAMs, the mGlu1 receptor NAMs appear to be better candidates for this role due to the following: (1) a number of highly potent, selective, and chemically diverse mGlu1 receptor NAMs to choose from; (2) availability of high-quality PET ligands to monitor target exposure; and (3) a rich pharmacological profile with a number of effects that can complement anti-addictive action (e.g., anxiolytic/antidepressant) and may also serve as additional pharmacodynamic readouts during the preclinical-to-clinical translation. We believe that the mGlu1 receptor NAMs have a significant value as potential tools for human experimental pharmacology that could help to validate methods used in preclinical research.
authors.affiliation: Institute of Pharmacology, Pavlov Medical University, St. Petersburg, Russia.
authors.forename: Olga A
authors.initials: OA
authors.lastname: Dravolina
authors.affiliation: Institute of Pharmacology, Pavlov Medical University, St. Petersburg, Russia.
authors.forename: Edwin
authors.initials: E
authors.lastname: Zvartau
authors.affiliation: Merz Pharmaceuticals, Frankfurt am Main, Germany.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Danysz
authors.affiliation: Institute of Pharmacology, Pavlov Medical University, St. Petersburg, Russia. anton.bespalov@exciva.com.|Exciva, Am Aukopf 14/1, 69118, Heidelberg, Germany. anton.bespalov@exciva.com.
authors.forename: Anton Y
authors.initials: AY
authors.lastname: Bespalov
mesh_terms: D000494:Allosteric Regulation / Q000187:drug effects / Q000502:physiology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage; D000928:Antidepressive Agents / Q000008:administration & dosage; D016503:Drug Delivery Systems / Q000379:methods*; D058999:Drug-Seeking Behavior / Q000187:drug effects / Q000502:physiology; D018690:Excitatory Amino Acid Agonists / Q000008:administration & dosage; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage; D006801:Humans; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019966:Substance-Related Disorders / Q000188:drug therapy* / Q000378:metabolism*
chemical_list: D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1
keywords: Addiction; Allosteric modulators; Cognition; Translational neuroscience; mGlu1 receptor