PMID- 28891448
OWN - NLM
STAT- MEDLINE
DCOM- 20190425
LR  - 20190425
IS  - 1873-4286 (Electronic)
IS  - 1381-6128 (Linking)
VI  - 23
IP  - 34
DP  - 2017
TI  - A Special Focus on Selexipag - Treatment of Pulmonary Arterial Hypertension.
PG  - 5191-5199
LID - 10.2174/1381612823666170908114227 [doi]
AB  - BACKGROUND: This review focuses on the treatment of pulmonary arterial 
      hypertension (PAH) with selexipag and compares its drug-related therapeutic 
      effects with those of prostacyclin analogues. METHODS: We searched the relevant 
      literature and summarized the current clinical trials concerning selexipag and 
      PAH. RESULTS: With only few cases per million, PAH is a rare disease, but when 
      untreated it can be life-threatening. PAH is linked to elevated levels of 
      endothelin (ET-1) and decreased levels of nitric oxide (NO) and prostacyclin 
      (PGI2). PAH-specific therapeutic approaches concentrate on these characteristics 
      with drugs targeting the endothelin- receptor (e.g. bosentan), 
      phosphodiesterase-5 (e.g. sildenafil) or the prostacyclin-receptor (e.g. 
      treprostinil). Recently, the new drug selexipag acting as a non-prostanoid 
      IP2-receptor agonist has been approved for PAH therapy. The active form of 
      selexipag (ACT-333679) was designed by the help of a medicinal chemistry program 
      and it was further modified by replacing the terminal carboxyl group with an 
      N-acylsulfonamide group to form the more stable oral drug, selexipag. Selexipag 
      has a high selectivity for the IP2-receptor and differs from conventional 
      prostacyclin analogues in its chemical structure. In the GRIPHON trial selexipag 
      was demonstrated to significantly improve the primary composite endpoint of death 
      or complications related to PAH (hazard ratio 0.6, 99% confidence interval, 0.46 
      to 0.78; P < 0.001) as well as exercise capacity in the form of the 6-minute walk 
      distance (12.0 m treatment effect, 99% confidence interval, 1 to 24; P = 0.003). 
      However, no significant reduction in all-cause mortality was achieved. Selexipag 
      has also shown promising results in combination therapy with phosphodiesterase-5 
      inhibitors (PDE-5i) and/or endothelin receptor antagonists (ERA). The most common 
      adverse effects (AEs), associated with selexipag, are headache, diarrhea, jaw 
      pain, and nausea. Nevertheless, Selexipag was generally well tolerated during the 
      GRIPHON trial. CONCLUSIONS: Selexipag is a valuable addition to PAH therapeutics 
      especially by reducing the PAH-related hospitalizations and thus improving 
      quality of life in PAH patients.
CI  - Copyright(c) Bentham Science Publishers; For any queries, please email at 
      epub@benthamscience.org.
FAU - Sorensen, Louise M
AU  - Sorensen LM
AD  - Institute of Biomedicine, Pharmacology, Aarhus University, Aarhus, Denmark.
FAU - Wehland, Markus
AU  - Wehland M
AD  - Clinic for Plastic, Aesthetic and Hand Surgery, Otto-von-Guericke-University 
      Magdeburg, Magdeburg, Germany.
FAU - Kruger, Marcus
AU  - Kruger M
AD  - Clinic for Plastic, Aesthetic and Hand Surgery, Otto-von-Guericke-University 
      Magdeburg, Magdeburg, Germany.
FAU - Simonsen, Ulf
AU  - Simonsen U
AD  - Institute of Biomedicine, Pharmacology, Aarhus University, Aarhus, Denmark.
FAU - Nassef, Mohamed Z
AU  - Nassef MZ
AD  - Clinic for Plastic, Aesthetic and Hand Surgery, Otto-von-Guericke-University 
      Magdeburg, Magdeburg, Germany.
FAU - Infanger, Manfred
AU  - Infanger M
AD  - Clinic for Plastic, Aesthetic and Hand Surgery, Otto-von-Guericke-University 
      Magdeburg, Magdeburg, Germany.
FAU - Grimm, Daniela
AU  - Grimm D
AD  - Institute of Biomedicine, Pharmacology, Aarhus University, Aarhus, Denmark.
AD  - Clinic for Plastic, Aesthetic and Hand Surgery, Otto-von-Guericke-University 
      Magdeburg, Magdeburg, Germany.
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United Arab Emirates
TA  - Curr Pharm Des
JT  - Current pharmaceutical design
JID - 9602487
RN  - 0 (Acetamides)
RN  - 0 (Antihypertensive Agents)
RN  - 0 (Prodrugs)
RN  - 0 (Pyrazines)
RN  - 5EXC0E384L (selexipag)
SB  - IM
MH  - Acetamides/chemistry/*therapeutic use
MH  - Animals
MH  - Antihypertensive Agents/chemistry/*therapeutic use
MH  - Clinical Trials as Topic/methods
MH  - Humans
MH  - Hypertension, Pulmonary/*drug therapy/metabolism
MH  - Prodrugs/chemistry/*therapeutic use
MH  - Pyrazines/chemistry/*therapeutic use
MH  - Treatment Outcome
OTO - NOTNLM
OT  - Pulmonary arterial hypertension
OT  - clinical trials
OT  - headache
OT  - non-prostanoid IP2-receptor agonist
OT  - prostacyclin analogues
OT  - selexipag
EDAT- 2017/09/12 06:00
MHDA- 2019/04/26 06:00
CRDT- 2017/09/12 06:00
PHST- 2017/06/28 00:00 [received]
PHST- 2017/09/04 00:00 [revised]
PHST- 2017/09/06 00:00 [accepted]
PHST- 2017/09/12 06:00 [pubmed]
PHST- 2019/04/26 06:00 [medline]
PHST- 2017/09/12 06:00 [entrez]
AID - CPD-EPUB-85650 [pii]
AID - 10.2174/1381612823666170908114227 [doi]
PST - ppublish
SO  - Curr Pharm Des. 2017;23(34):5191-5199. doi: 10.2174/1381612823666170908114227.