PMID- 31284863
OWN - NLM
STAT- MEDLINE
DCOM- 20191028
LR  - 20200225
IS  - 1873-4294 (Electronic)
IS  - 1568-0266 (Print)
IS  - 1568-0266 (Linking)
VI  - 19
IP  - 16
DP  - 2019
TI  - Overcoming the Psychiatric Side Effects of the Cannabinoid CB1 Receptor 
      Antagonists: Current Approaches for Therapeutics Development.
PG  - 1418-1435
LID - 10.2174/1568026619666190708164841 [doi]
AB  - The Cannabinoid CB1 Receptor (CB1R) is involved in a variety of physiological 
      pathways and has long been considered a golden target for therapeutic 
      manipulation. A large body of evidence in both animal and human studies suggests 
      that CB1R antagonism is highly effective for the treatment of obesity, metabolic 
      disorders and drug addiction. However, the first-in-class CB1R antagonist/inverse 
      agonist, rimonabant, though demonstrating effectiveness for obesity treatment and 
      smoking cessation, displays serious psychiatric side effects, including anxiety, 
      depression and even suicidal ideation, resulting in its eventual withdrawal from 
      the European market. Several strategies are currently being pursued to circumvent 
      the mechanisms leading to these side effects by developing neutral antagonists, 
      peripherally restricted ligands, and allosteric modulators. In this review, we 
      describe the progress in the development of therapeutics targeting the CB1R in 
      the last two decades.
CI  - Copyright(c) Bentham Science Publishers; For any queries, please email at 
      epub@benthamscience.net.
FAU - Nguyen, Thuy
AU  - Nguyen T
AD  - Research Triangle Institute, Research Triangle Park, NC 27709, United States.
FAU - Thomas, Brian F
AU  - Thomas BF
AD  - Research Triangle Institute, Research Triangle Park, NC 27709, United States.
FAU - Zhang, Yanan
AU  - Zhang Y
AD  - Research Triangle Institute, Research Triangle Park, NC 27709, United States.
LA  - eng
GR  - R01 DA040460/DA/NIDA NIH HHS/United States
GR  - R01 DA040693/DA/NIDA NIH HHS/United States
GR  - R03 DA045910/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Review
PL  - United Arab Emirates
TA  - Curr Top Med Chem
JT  - Current topics in medicinal chemistry
JID - 101119673
RN  - 0 (Antipsychotic Agents)
RN  - 0 (Cannabinoid Receptor Antagonists)
RN  - 0 (Receptor, Cannabinoid, CB1)
SB  - IM
MH  - Animals
MH  - Antipsychotic Agents/*adverse effects/pharmacology
MH  - Cannabinoid Receptor Antagonists/*adverse effects/pharmacology
MH  - Humans
MH  - Obesity/*drug therapy/metabolism
MH  - Receptor, Cannabinoid, CB1/*antagonists & inhibitors/metabolism
MH  - *Smoking Cessation
PMC - PMC6771026
MID - NIHMS1052222
OTO - NOTNLM
OT  - Allosteric modulators
OT  - CB1 receptor
OT  - Neutral antagonists
OT  - Peripherally restricted antagonists
OT  - Psychiatric side effects
OT  - Therapeutics development.
COIS- CONFLICT OF INTEREST The authors confirm that this article has no conflict of 
      interest.
EDAT- 2019/07/10 06:00
MHDA- 2019/10/29 06:00
PMCR- 2020/01/01
CRDT- 2019/07/10 06:00
PHST- 2018/10/10 00:00 [received]
PHST- 2018/11/08 00:00 [revised]
PHST- 2018/11/15 00:00 [accepted]
PHST- 2019/07/10 06:00 [pubmed]
PHST- 2019/10/29 06:00 [medline]
PHST- 2019/07/10 06:00 [entrez]
PHST- 2020/01/01 00:00 [pmc-release]
AID - CTMC-EPUB-99469 [pii]
AID - 10.2174/1568026619666190708164841 [doi]
PST - ppublish
SO  - Curr Top Med Chem. 2019;19(16):1418-1435. doi: 10.2174/1568026619666190708164841.