PMID- 20663054
OWN - NLM
STAT- MEDLINE
DCOM- 20101122
LR  - 20131121
IS  - 1365-2982 (Electronic)
IS  - 1350-1925 (Linking)
VI  - 22
IP  - 8
DP  - 2010 Aug
TI  - Treatment of gastro-esophageal reflux disease: the new kids to block.
PG  - 836-40
LID - 10.1111/j.1365-2982.2010.01537.x [doi]
AB  - Refractory gastro-esophageal reflux disease (GERD), defined as persistent 
      symptoms despite proton pump inhibitor (PPI) therapy, is an increasingly 
      prevalent condition and is becoming a major challenge for the clinician. Since 
      non-acidic reflux may be associated with symptoms persisting during PPI 
      treatment, the lower esophageal sphincter (LES), the most important barrier 
      protecting against reflux, has become an important target for the treatment of 
      (refractory) GERD. Preclinical research has identified several receptors that are 
      involved in the control of transient lower esophageal sphincter relaxations 
      (TLESRs), the predominant mechanism of both acid and non-acidic reflux events, 
      and several drugs have now been tested in humans. The GABA(B) agonist baclofen 
      has demonstrated to effectively reduce the rate of TLESRs and the amount of 
      reflux in both GERD patients and healthy volunteers. Nevertheless, the occurrence 
      of central side effects limits its clinical use for the treatment of GERD. 
      Several analogues are being developed to overcome this limitation and have shown 
      promising results. Additionally, metabotropic glutamate receptor 5 (mGluR5) 
      receptor antagonists have shown to reduce both acid and non-acidic reflux in GERD 
      patients and several molecules are currently being evaluated. Although CB(1) 
      antagonists have been shown to reduce TLESRs, they are also associated with 
      central side effects, limiting their clinical applicability. Despite the 
      identification of several potentially interesting drugs, the main challenge for 
      the future remains the reduction of central side effects. Moreover, future 
      studies will need to demonstrate the efficacy of these treatments in patients 
      with refractory GERD.
FAU - Blondeau, K
AU  - Blondeau K
AD  - Center for gastroenterological research, KULeuven, Belgium. 
      Kathleen.Blondeau@med.kuleuven.be
LA  - eng
PT  - Journal Article
PT  - Review
PL  - England
TA  - Neurogastroenterol Motil
JT  - Neurogastroenterology and motility
JID - 9432572
RN  - 0 (Cannabinoid Receptor Agonists)
RN  - 0 (GABA-B Receptor Agonists)
RN  - 0 (GRM5 protein, human)
RN  - 0 (Proton Pump Inhibitors)
RN  - 0 (Receptor, Metabotropic Glutamate 5)
RN  - 0 (Receptors, Metabotropic Glutamate)
SB  - IM
MH  - Cannabinoid Receptor Agonists
MH  - Esophageal Sphincter, Lower/drug effects
MH  - GABA-B Receptor Agonists
MH  - Gastroesophageal Reflux/*drug therapy
MH  - Humans
MH  - Proton Pump Inhibitors/pharmacology/therapeutic use
MH  - Receptor, Metabotropic Glutamate 5
MH  - Receptors, Metabotropic Glutamate/antagonists & inhibitors
EDAT- 2010/07/29 06:00
MHDA- 2010/12/14 06:00
CRDT- 2010/07/29 06:00
PHST- 2010/07/29 06:00 [entrez]
PHST- 2010/07/29 06:00 [pubmed]
PHST- 2010/12/14 06:00 [medline]
AID - NMO1537 [pii]
AID - 10.1111/j.1365-2982.2010.01537.x [doi]
PST - ppublish
SO  - Neurogastroenterol Motil. 2010 Aug;22(8):836-40. doi: 
      10.1111/j.1365-2982.2010.01537.x.