Modulation of Serotonin in PAH
Mandy MacLean, University of Glasgow Scotland
PVRI – Pulmonary Vascular Research Institute
Rodatristat Ethyl Publications
Once Daily Oral Dosing of RodatristatEthyl (RVT-1201) Achieves Reductions in Serotonin Biosynthesis Comparable to Those Associated with Reversal of Vascular Remodeling in PAH Animal Models
22 October 2019 CHEST Annual Meeting 2019; New Orleans, LA
Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics After Repeated Once or Twice Daily RVT-1201, a TPH Inhibitor for Treatment of PAH
1 October 2019 European Respiratory Society (ERS) International Congress; Madrid, Spain
Optimization and Validation of a LC-MS/MS Method for Peripheral Serotonin (5-HT) as a Pharmacodynamic Biomarker of Treatment with Tryptophan Hydroxylase Inhibitors
3 June 2019 67th Conference on Mass Spectrometry and Allied Topics; Atlanta, GA
Translational Analysis of RVT-1201 Nonclinical and Clinical Pharmacokinetic and Pharmacodynamic Biomarker Data to Predict Clinical Dose of a Novel TPH Inhibitor for Treatment of Pulmonary Arterial Hypertension
2 February 2019 13th PVRI Annual World Congress on PVD; Barcelona, Spain.
Tryptophan hydroxylase 1 Inhibition Impacts Pulmonary Vascular Remodeling in Two Rat Models of Pulmonary Hypertension
J Pharmacol Exp Ther. 2017 Feb;360(2):267-279.
Tryptophan Hydroxylase (TPH) Platform Publications
The Serotonin Hypothesis of PAH – Reviews
Recent advances in pulmonary arterial hypertension
F1000Res. 2018 Jul 24;7.
The serotonin hypothesis in pulmonary hypertension revisited: targets for novel therapies (2017 Grover Conference Series)
Pulm Circ. 2018 Apr-Jun;8(2):2045894018759125.
Drug-induced pulmonary arterial hypertension: a primer for clinicians and scientists
Am J Physiol Lung Cell Mol Physiol. 2018 Jun 1;314(6):L967-L983.
Review of the Ongoing Story of Appetite Suppressants, Serotonin Pathway, and Pulmonary Vascular Disease
Am J Cardiol. 2016 May 15;117(10):1691-1696.
The serotonin hypothesis of pulmonary hypertension revisited
Adv Exp Med Biol. 2010;661:309-22.
Serotonin and pulmonary hypertension–from bench to bedside?
Curr Opin Pharmacol. 2009 Jun;9(3):281-6.
Pulmonary hypertension: therapeutic targets within the serotonin system.
Br J Pharmacol. 2008 Oct;155(4):455-62.
Peripheral Serotonin Modulation with Tph1 Inhibitors
GPCRs in pulmonary arterial hypertension: tipping the balance
Br J Pharmacol. 2018 Aug;175(15):3063-3079.
Peripheral Serotonin Synthesis as a New Drug Target
Trends Pharmacol Sci. 2018 Jun;39(6):560-572.
Tryptophan Hydroxylase 1 Inhibition Impacts Pulmonary Vascular Remodeling in Two Rat Models of Pulmonary Hypertension
J Pharmacol Exp Ther. 2017 Feb;360(2):267-279.
Clinical Data Linking Serotonin to PAH
Anorexigens and pulmonary hypertension in the United States: results from the surveillance of North American pulmonary hypertension
Chest. 2000 Mar;117(3):870-4.
Appetite-suppressant drugs and the risk of primary pulmonary hypertension
International Primary Pulmonary Hypertension Study Group. N Engl J Med. 1996 Aug 29;335(9):609-16.
Increased plasma serotonin in primary pulmonary hypertension
Am J Med. 1995 Sep;99(3):249-54.
Preclinical Data Linking Serotonin to PAH
Imatinib attenuates hypoxia-induced pulmonary arterial hypertension pathology via reduction in 5-hydroxytryptamine through inhibition of tryptophan hydroxylase 1 expression
Am J Respir Crit Care Med. 2013 Jan 1;187(1):78-89.
Gene therapy by targeted adenovirus-mediated knockdown of pulmonary endothelial Tph1 attenuates hypoxia-induced pulmonary hypertension
Mol Ther. 2012 Aug;20(8):1516-28.
Converging evidence in support of the serotonin hypothesis of dexfenfluramine-induced pulmonary hypertension with novel transgenic mice
Circulation. 2008 Jun 3;117(22):2928-37.
Effect of tryptophan hydroxylase 1 deficiency on the development of hypoxia-induced pulmonary hypertension
Hypertension. 2007 Jan;49(1):232-6.
Transgenic mice overexpressing the 5-hydroxytryptamine transporter gene in smooth muscle develop pulmonary hypertension
Circ Res. 2006 May 26;98(10):1323-30.
Cross talk between endothelial and smooth muscle cells in pulmonary hypertension: critical role for serotonin-induced smooth muscle hyperplasia
Circulation. 2006 Apr 18;113(15):1857-64.
Patient Engagement Publications
A Framework for Engaging PAH Patients in the Drug Development Process
5 September 2019 Pulmonary Hypertension Association’s Annual PH Professional Network (PHPN) Symposium; Washington, D.C.
