PMID- 23675941
OWN - NLM
STAT- MEDLINE
DCOM- 20140115
LR  - 20211021
IS  - 1873-4294 (Electronic)
IS  - 1568-0266 (Print)
IS  - 1568-0266 (Linking)
VI  - 13
IP  - 11
DP  - 2013
TI  - Predictive in silico studies of human 5-hydroxytryptamine receptor subtype 2B 
      (5-HT2B) and valvular heart disease.
PG  - 1353-62
AB  - Serotonin (5-hydroxytryptamine, 5-HT) receptors are neuromodulator 
      neurotransmitter receptors which when activated trigger a signal transduction 
      cascade within cells resulting in cell-cell communication. 5-hydroxytryptamine 
      receptor 2B (5-HT2B) is a subtype of the seven members of 5-hydroxytrytamine 
      receptors family which is the largest member of the super family of 
      7-transmembrane G-protein coupled receptors (GPCRs). Not only do 5-HT receptors 
      play physiological roles in the cardiovascular system, gastrointestinal and 
      endocrine function as well as the central nervous system, but they also play a 
      role in behavioral functions. In particular 5-HT2B receptor is widely spread with 
      regards to its distribution throughout bodily tissues and is expressed at high 
      levels in the lungs, peripheral tissues, liver, kidneys and prostate, just to 
      name a few. Hence 5-HT2B participates in multiple biological functions including 
      CNS regulation, regulation of gastrointestinal motality, cardiovascular 
      regulation and 5-HT transport system regulation. While 5-HT2B is a viable drug 
      target and has therapeutic indications for treating obesity, psychosis, 
      Parkinson's disease etc. there is a growing concern regarding adverse drug 
      reactions, specifically valvulopathy associated with 5-HT2B agonists. Due to the 
      sequence homology experienced by 5-HT2 subtypes there is also a concern regarding 
      the off-target effects of 5-HT2A and 5-HT2C agonists. The concepts of sensitivity 
      and subtype selectivity are of paramount importance and now can be tackled with 
      the aid of in silico studies, especially cheminformatics, to develop models to 
      predict valvulopathy associated toxicity of drug candidates prior to clinical 
      trials. This review has highlighted three in silico approaches thus far that have 
      been successful in either predicting 5-HT2B toxicity of molecules or identifying 
      important interactions between 5-HT2B and drug molecules that bring about 
      valvulopathy related toxicities.
FAU - Reid, Terry-Elinor
AU  - Reid TE
AD  - Molecular Modeling and Drug Discovery Core for District of Columbia Developmental 
      Center for AIDS Research (DCD-CFAR), Washington DC 20059, USA.
FAU - Kumar, Krishna
AU  - Kumar K
FAU - Wang, Xiang Simon
AU  - Wang XS
LA  - eng
GR  - G12 MD007597/MD/NIMHD NIH HHS/United States
GR  - P30 AI087714/AI/NIAID NIH HHS/United States
GR  - P30AI087714/AI/NIAID NIH HHS/United States
GR  - G12MD007597/MD/NIMHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, P.H.S.
PT  - Review
PL  - United Arab Emirates
TA  - Curr Top Med Chem
JT  - Current topics in medicinal chemistry
JID - 101119673
RN  - 0 (Receptor, Serotonin, 5-HT2A)
RN  - 0 (Receptor, Serotonin, 5-HT2B)
RN  - 0 (Receptor, Serotonin, 5-HT2C)
RN  - 0 (Serotonin 5-HT2 Receptor Agonists)
RN  - 0 (Serotonin 5-HT2 Receptor Antagonists)
RN  - 333DO1RDJY (Serotonin)
SB  - IM
MH  - Computer Simulation
MH  - Drug Design
MH  - *Drug Evaluation, Preclinical
MH  - Heart Valve Diseases/chemically induced/*prevention & control
MH  - Humans
MH  - *Models, Molecular
MH  - Quantitative Structure-Activity Relationship
MH  - Receptor, Serotonin, 5-HT2A/chemistry
MH  - Receptor, Serotonin, 5-HT2B/*chemistry/metabolism
MH  - Receptor, Serotonin, 5-HT2C/chemistry
MH  - Serotonin/metabolism
MH  - Serotonin 5-HT2 Receptor Agonists/*adverse effects/chemistry
MH  - Serotonin 5-HT2 Receptor Antagonists/chemistry
MH  - Signal Transduction
PMC - PMC4086739
MID - NIHMS607291
EDAT- 2013/05/17 06:00
MHDA- 2014/01/16 06:00
PMCR- 2014/07/08
CRDT- 2013/05/17 06:00
PHST- 2012/11/19 00:00 [received]
PHST- 2013/04/22 00:00 [accepted]
PHST- 2013/05/17 06:00 [entrez]
PHST- 2013/05/17 06:00 [pubmed]
PHST- 2014/01/16 06:00 [medline]
PHST- 2014/07/08 00:00 [pmc-release]
AID - CTMC-EPUB-20130509-9 [pii]
AID - 10.2174/15680266113139990039 [doi]
PST - ppublish
SO  - Curr Top Med Chem. 2013;13(11):1353-62. doi: 10.2174/15680266113139990039.