AVE1625, a cannabinoid CB1 receptor antagonist, as a co-treatment with antipsychotics for schizophrenia: improvement in cognitive function and reduction of antipsychotic-side effects in rodents

Black, Mark D.; Stevens, Rachel J.; Rogacki, Nancy; Featherstone, Robert E.; Senyah, Yaw; Giardino, Odessa; Borowsky, Beth; Stemmelin, Jeanne; Cohen, Caroline; Pichat, Philippe; Arad, Michal; Barak, Segev; Levie, Amaya De; Weiner, Ina; Griebel, Guy; Varty, Geoffrey B.

doi:10.1007/s00213-010-2124-0

Cited by 46 publications

(31 citation statements)

References 62 publications

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“…In addition, AM251 reduced urocortin1 microinjection-and nicotine abstinence-induced anxieties [69,70]. Other antagonists (AM281, AM4113, and AVE1625) did not affect anxiety [66,[71][72][73].…”

Section: Decreased Endocannabinoid Activitymentioning

confidence: 99%

Interactions Between Cannabinoid Signaling and Anxiety: A Comparative Analysis of Intervention Tools and Behavioral Effects

Aliczki

Haller

2015

Cannabinoid Modulation of Emotion, Memory, and Motivation

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Cannabinoid signaling is believed to decrease anxiety, albeit the conflicting nature of evidence is generally acknowledged. Here we provide a comprehensive overview of available findings by grouping them according to the tools that have been used to modulate cannabinoid signaling. The systemic administration of cannabinoid receptor agonists and antagonists led to the most conflicting findings; such treatments may increase, decrease, or leave anxiety unaffected. In addition, antagonists and agonists had similar effects in many instances including their biphasic effects. The effects of genetic manipulations, cannabinoid synthesis or reuptake inhibition as well as the effects of local brain treatments with cannabinoid ligands appear more consistent. We suggest that systemically administered receptor ligands affect cannabinoid signaling globally and as such lack the spatial and temporal specificity of endocannabinoid signaling. By contrast, gene disruption and the indirect modulation of endocannabinoid availability affect ongoing (natural) processes and lead to more specific and consistent effects. Local brain treatments whit receptor ligands are spatially restricted which increases the consistency of findings, but also reveals that cannabinoids affect anxiety in a brain area-specific manner, which further explains the inconsistency of findings with systemically injected ligands. Environmental conditions have a large impact on effects with all techniques, suggesting that endocannabinoid signaling affects coping with environmental challenges rather than unconditionally decreasing anxiety. The relationship between cannabinoid signaling, anxiety and coping styles is largely understudied, but holds great promise for understanding the roles of cannabinoids in behavioral control and may broaden their therapeutic implications.

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Section: Decreased Endocannabinoid Activitymentioning

confidence: 99%

Interactions Between Cannabinoid Signaling and Anxiety: A Comparative Analysis of Intervention Tools and Behavioral Effects

Aliczki

Haller

2015

Cannabinoid Modulation of Emotion, Memory, and Motivation

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“…The first CB 1 -selective antagonist/inverse agonist, rimonabant (SR141716, Acomplia™ (Sanofi-Aventis)) (Rinaldi-Carmona et al, 1994), received approval from the European Medical Agency as an adjunct to diet and exercise for treating obesity (Janero and Makriyannis, 2009). Antagonists of CB 1 have been explored as potential therapeutics for obesity-related metabolic disorders (Mazier et al, 2015), mental illness (Black et al, 2011; Rubino et al, 2015), liver fibrosis (Mallat et al, 2013) and nicotine addiction (Schindler et al, 2016). However, rimonabant and other ligands in its class were not approved in the United States due to concerns about adverse events, such as increased anxiety, depression, and suicidal ideation.…”

Section: Introductionmentioning

confidence: 99%

Crystal Structure of the Human Cannabinoid Receptor CB1

Hua

Vemuri

et al. 2016

Cell

501

488

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SUMMARY Cannabinoid receptor 1 (CB1) is the principal target of Δ9-tetrahydrocannabinol (THC), a psychoactive chemical from Cannabis sativa with a wide range of therapeutic applications and a long history of recreational use. CB1 is activated by endocannabinoids, and is a promising therapeutic target for pain management, inflammation, obesity and substance abuse disorders. Here, we present the 2.8 Å crystal structure of human CB1 in complex with AM6538, a stabilizing antagonist, synthesized and characterized for this structural study. The structure of the CB1-AM6538 complex reveals key features of the receptor and critical interactions for antagonist binding. In combination with functional studies and molecular modeling, the structure provides insight into the binding mode of naturally occurring CB1 ligands, such as THC, and synthetic cannabinoids. This enhances our understanding of the molecular basis for the physiological functions of CB1 and provides new opportunities for the design of next-generation CB1-targeting pharmaceuticals.

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“…Cannabinoids also increase dopamine cell firing, an effect opposite to that produced by amphetamine or cocaine but similar to the effect of antipsychotics. Cannabinoid receptor knock-out mice have been proposed as an animal model of schizophrenia (Black et al 2011;Fritzsche 2001). On the other hand, chronic use of cannabinoids is associated with schizophrenic-like attentiondependent deficits in PPI (Kedzior and Martin-Iverson 2006;Scholes and Martin-Iverson 2009), and acute use of cannabis is associated with other cognitive dysfunctions similar to those observed in schizophrenia (Long et al 2006;Solowij and Michie 2007).…”

Section: Discussionmentioning

confidence: 95%

Corticosteroid dependent and independent effects of a cannabinoid agonist on core temperature, motor activity, and prepulse inhibition of the acoustic startle reflex in Wistar rats

2011

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AVE1625, a cannabinoid CB1 receptor antagonist, as a co-treatment with antipsychotics for schizophrenia: improvement in cognitive function and reduction of antipsychotic-side effects in rodents

Cited by 46 publications

References 62 publications

Interactions Between Cannabinoid Signaling and Anxiety: A Comparative Analysis of Intervention Tools and Behavioral Effects

Interactions Between Cannabinoid Signaling and Anxiety: A Comparative Analysis of Intervention Tools and Behavioral Effects

Crystal Structure of the Human Cannabinoid Receptor CB1

Corticosteroid dependent and independent effects of a cannabinoid agonist on core temperature, motor activity, and prepulse inhibition of the acoustic startle reflex in Wistar rats

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