Cannabinoid Receptor Signaling in Central Regulation of Feeding Behavior: A Mini-Review

The endocannabinoid system (ECS) is a highly versatile signaling system within the nervous system. Despite its widespread localization, its functions within the context of distinct neural processes are very well discernable and specific. This is remarkable, and the question remains as to how such specificity is achieved. One key player in the ECS is the cannabinoid type 1 receptor (CB1), a G protein–coupled receptor characterized by the complexity of its cell-specific expression, cellular and subcellular localization, and its adaptable regulation of intracellular signaling cascades. CB1 receptors are involved in different synaptic and cellular plasticity processes and in the brain’s bioenergetics in a context-specific manner. CB2 receptors are also important in several processes in neurons, glial cells, and immune cells of the brain. As polymorphisms in ECS components, as well as external impacts such as stress and metabolic challenges, can both lead to dysregulated ECS activity and subsequently to possible neuropsychiatric disorders, pharmacological intervention targeting the ECS is a promising therapeutic approach. Understanding the neurobiology of cannabinoid receptor signaling in depth will aid optimal design of therapeutic interventions, minimizing unwanted side effects.

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Discovery of Orexant and Anorexant Agents with Indazole Scaffold Endowed with Peripheral Antiedema Activity

Biomolecules ◽

10.3390/biom9090492 ◽

2019 ◽

Vol 9 (9) ◽

pp. 492 ◽

Cited By ~ 5

Author(s):

Dimmito ◽

Stefanucci ◽

Pieretti ◽

Minosi ◽

Dvorácskó ◽

...

Keyword(s):

Feeding Behavior ◽

Cannabinoid Receptors ◽

Cannabinoid Receptor ◽

Methyl Esters ◽

Endocannabinoid System ◽

Tail Flick ◽

Binding Assays ◽

Tail Flick Test

The endocannabinoid system represents an integrated neuronal network involved in the control of several organisms’ functions, such as feeding behavior. A series of hybrids of 5-(4-chlorophenyl)-1-(2,4-dichloro-phenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide (mimonabant), a well-known inverse agonist of the type-1 cannabinoid receptor (CB1), once used as an antiobesity drug, and the N-(2S)-substitutes of 1-[(4-fluorophenyl)methyl]indazole-3-carboxamide with 1-amino-3-methyl-1-oxobutane (AB-Fubinaca), 1-amino-3,3-dimethyl-1-oxobutane (ADB-Fubinaca), and 3-methylbutanoate (AMB-Fubinaca), endowed with potent agonistic activity towards cannabinoid receptors CB1 and CB2 were in solution as C-terminal amides, acids, methyl esters and N-methyl amides. These compounds have been studied by binding assays to cannabinoid receptors and by functional receptor assays, using rat brain membranes in vitro. The most active among them as an agonist, (S)-1-(2,4-dichlorobenzyl)-N-(3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl)-1H-indazole-3-carboxamide (LONI11), and an antagonist, (S)-2-(1-(2,4-dichlorobenzyl)-1H-indazole-3-carboxamido)-3-methylbutanoic acid (LONI4), were tested in vivo in mic, to evaluate their ability to stimulate or suppress feeding behavior after intraperitoneal (i.p.) administration. For a LONI11 formalin test and a tail flick test after an administration by the subcutaneous (s.c.) and intracerebroventricular (i.c.v.) routes, respectively, were also carried out in vivo in mice to investigate the antinociceptive property at the central and peripheral levesl. We observed a significant orexant effect for LONI11 and an intense anorexant effect for (S)-methyl 2-(1-(2,4-dichlorobenzyl)-1H-indazole-3-carboxamido)-3,3-dimethylbutanoate (LONI2) and LONI4. In zymosan-induced edema and hyperalgesia, LONI11 reduced the percent of paw volume increase and paw latency after s.c. administration, also suggesting a possible peripheral anti-inflammatory activity.

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Cannabinoid Receptor Signaling Directly Inhibits Thermogenesis and Alters Expression of Adiponectin and Visfatin

Hormone and Metabolic Research ◽

10.1055/s-2006-925401 ◽

2006 ◽

Vol 38 (5) ◽

pp. 356-358 ◽

Cited By ~ 55

Author(s):

N. Perwitz ◽

M. Fasshauer ◽

J. Klein

Keyword(s):

Cannabinoid Receptor ◽

Receptor Signaling

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Cannabinoid Receptor–Interacting Protein 1a Modulates CB1 Receptor Signaling and Regulation

Molecular Pharmacology ◽

10.1124/mol.114.096495 ◽

2015 ◽

Vol 87 (4) ◽

pp. 747-765 ◽

Cited By ~ 32

Author(s):

Tricia H. Smith ◽

Lawrence C. Blume ◽

Alex Straiker ◽

Jordan O. Cox ◽

Bethany G. David ◽

...

Keyword(s):

Cannabinoid Receptor ◽

Cb1 Receptor ◽

Receptor Signaling ◽

Interacting Protein

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Cannabinoid signaling in health and disease

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2016-0346 ◽

2017 ◽

Vol 95 (4) ◽

pp. 311-327 ◽

Cited By ~ 49

Author(s):

Yan Lu ◽

Hope D. Anderson

Keyword(s):

Side Effects ◽

Cannabis Sativa ◽

Cannabinoid Receptor ◽

Therapeutic Potential ◽

Endocannabinoid System ◽

Receptor Signaling ◽

Safety And Efficacy ◽

Health And Disease ◽

Endogenous Cannabinoid ◽

Umbrella Group

Cannabis sativa has long been used for medicinal purposes. To improve safety and efficacy, compounds from C. sativa were purified or synthesized and named under an umbrella group as cannabinoids. Currently, several cannabinoids may be prescribed in Canada for a variety of indications such as nausea and pain. More recently, an increasing number of reports suggest other salutary effects associated with endogenous cannabinoid signaling including cardioprotection. The therapeutic potential of cannabinoids is therefore extended; however, evidence is limited and mechanisms remain unclear. In addition, the use of cannabinoids clinically has been hindered due to pronounced psychoactive side effects. This review provides an overview on the endocannabinoid system, including known physiological roles, and conditions in which cannabinoid receptor signaling has been implicated.

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