Overcoming Treatment Resistant PTSD Nightmares With an Endocannabinoid Receptor Agonist

2008 ◽  
Author(s):  
George Fraser
Keyword(s):  
Receptor Agonist ◽  
Treatment Resistant ◽  
Endocannabinoid Receptor

scholarly journals (2R,6R)-hydroxynorketamine exerts mGlu2receptor-dependent antidepressant actions

2019 ◽  
Vol 116 (13) ◽  
pp. 6441-6450 ◽  
Author(s):  
Panos Zanos ◽  
Jaclyn N. Highland ◽  
Brent W. Stewart ◽  
Polymnia Georgiou ◽  
Carleigh E. Jenne ◽  
...  
Keyword(s):  
Receptor Agonist ◽  
Metabotropic Glutamate Receptor ◽  
Antidepressant Drug ◽  
Antidepressant Drugs ◽  
Gamma Oscillations ◽  
Quantitative Eeg ◽  
Drug Candidate ◽  
Receptor Subtypes ◽  
Treatment Resistant ◽  
Gamma Range

Currently approved antidepressant drugs often take months to take full effect, and ∼30% of depressed patients remain treatment resistant. In contrast, ketamine, when administered as a single subanesthetic dose, exerts rapid and sustained antidepressant actions. Preclinical studies indicate that the ketamine metabolite (2R,6R)-hydroxynorketamine [(2R,6R)-HNK] is a rapid-acting antidepressant drug candidate with limited dissociation properties and abuse potential. We assessed the role of group II metabotropic glutamate receptor subtypes 2 (mGlu2) and 3 (mGlu3) in the antidepressant-relevant actions of (2R,6R)-HNK using behavioral, genetic, and pharmacological approaches as well as cortical quantitative EEG (qEEG) measurements in mice. Both ketamine and (2R,6R)-HNK prevented mGlu2/3receptor agonist (LY379268)-induced body temperature increases in mice lacking theGrm3, but notGrm2, gene. This action was not replicated by NMDA receptor antagonists or a chemical variant of ketamine that limits metabolism to (2R,6R)-HNK. The antidepressant-relevant behavioral effects and 30- to 80-Hz qEEG oscillation (gamma-range) increases resultant from (2R,6R)-HNK administration were prevented by pretreatment with an mGlu2/3receptor agonist and absent in mice lacking theGrm2, but notGrm3−/−, gene. Combined subeffective doses of the mGlu2/3receptor antagonist LY341495 and (2R,6R)-HNK exerted synergistic increases on gamma oscillations and antidepressant-relevant behavioral actions. These findings highlight that (2R,6R)-HNK exerts antidepressant-relevant actions via a mechanism converging with mGlu2receptor signaling and suggest enhanced cortical gamma oscillations as a marker of target engagement relevant to antidepressant efficacy. Moreover, these results support the use of (2R,6R)-HNK and inhibitors of mGlu2receptor function in clinical trials for treatment-resistant depression either alone or in combination.

scholarly journals Thrombocytopenia associated with clonidine in a case of clozapine-induced sialorrhea

2020 ◽  
Vol 10 (1) ◽  
pp. 34-37
Author(s):  
Jonathan G. Leung ◽  
Jade L. Kutzke ◽  
Robert J. Morgan ◽  
Kathryn M. Schak
Keyword(s):  
Adverse Event ◽  
Adverse Events ◽  
Aspiration Pneumonia ◽  
Schizoaffective Disorder ◽  
Adrenergic Receptor ◽  
Receptor Agonist ◽  
Severe Neutropenia ◽  
Treatment Resistant ◽  
The Us ◽  
Adrenergic Receptor Agonist

Abstract Clozapine is approved by the US Food and Drug Administration for treatment-resistant schizophrenia and mitigation of suicidality in patients with schizophrenia or schizoaffective disorder. Clozapine requires monitoring of adverse events, such as hypotension, myocarditis, cardiomyopathy, seizures, severe neutropenia, and gastrointestinal hypomotility. Sialorrhea is another adverse event that can be bothersome for patients and result in nonadherence or the development of aspiration pneumonia. Clonidine, an α2A adrenergic receptor agonist, is one medication option that can reduce or eliminate sialorrhea. Clonidine is generally well tolerated but can contribute to hypotension and sedation. One adverse event associated with clonidine not described in the literature is thrombocytopenia. Reported is a case of clonidine-associated thrombocytopenia when used for the treatment of clozapine-induced sialorrhea.

MKC-733, a selective 5-HT3 receptor agonist, stimulates fasting human antral motility

2001 ◽  
Vol 120 (5) ◽  
pp. A460-A461 ◽  
Author(s):  
N COLEMAN ◽  
J WRIGHT ◽  
M PARKER ◽  
R SPILLER
Keyword(s):  
Receptor Agonist ◽  
Antral Motility

1197: AT-Home Efficacy of an Intranasally Administered Melanocortin Receptor Agonist, PT-141, In Men with Erectile Dysfunction (ED)

2004 ◽  
Vol 171 (4S) ◽  
pp. 316-316
Author(s):  
Hunter Wessells ◽  
Harin Padma-Nathan ◽  
Jacob Rajfer ◽  
Robert Feldman ◽  
Raymond Rosen ◽  
...  
Keyword(s):  
Erectile Dysfunction ◽  
Receptor Agonist ◽  
Melanocortin Receptor ◽  
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