Understanding gene-environment interactions leads to possible preventive treatment
An inhaled form of a high blood pressure medication has potential to treat certain types of anxiety as well as pain, according to a new study by the Centre for Addiction and Mental Health (CAMH).
Anxiety disorders are usually treated with different types of medications, such as antidepressants, and psychotherapy. Amiloride is a medication offering a new approach, as a short-acting nasal spray that could be used to prevent an anxiety attack.
“Inhaled amiloride may prove to have benefits for panic disorder, which is typically characterized by spells of shortness of breath and fear, when people feel anxiety levels rising,” says lead author Dr. Marco Battaglia, Associate Chief of Child and Youth Psychiatry and Clinician Scientist in the Campbell Family Mental Health Research Institute at CAMH.
The study was based on understanding the key physiological changes in brain functioning that are linked to anxiety and pain sensitivity. The researchers then tested a molecule, amiloride, which targets this functioning.
Amiloride was inhaled so that it could immediately access the brain. The study showed that it reduced the physical respiratory signs of anxiety and pain in a preclinical model of illness. This therapeutic effect didn’t occur when amiloride was administered in the body, as it didn’t cross the blood-brain barrier and did not reach the brain.
Results were published in the Journal of Psychopharmacology.
The role of early life adversity
The study is based on years of research into how a person’s early life experiences affect their genes, says Dr. Battaglia. Childhood adversity, such as loss or separation from parents, increases the risk of anxiety disorders and pain, among other health issues.
At a molecular level, these negative life experiences are linked to changes in some genes of the ASIC (acid-sensing-ion-channels) family. While the DNA itself doesn’t change, the way it functions is affected.
DNA is converted into working proteins through a process called gene expression. As a result of childhood adversity, some ASIC genes showed increased expression and epigenomic changes. (“Epigenomic” refers to changes in gene regulation that can inherited by children). Overlapping genetic changes were also seen in blood taken from twins who responded to specific tests designed to provoke panic.
These genetic changes are linked to physical symptoms. Breathing can be affected, due to over-sensitivity to higher carbon dioxide levels in the air. In such situations, a person might hyperventilate and experience growing anxiety. Preclinical and human data are strikingly similar in this regard. “As a treatment, amiloride turned out to be very effective preclinically,” says Dr. Battaglia.
The next step in his research is to test whether it eases anxiety symptoms. Dr. Battaglia is now launching a pilot clinical trial, supported through a seed grant from CAMH’s new Discovery Fund. Collaborators at the University of Utah are testing the drug’s safety.
Amiloride has been used as an oral treatment for decades for hypertension, and as an inhaled spray in a few experimental studies of cystic fibrosis, he notes. The researchers are therefore further ahead than if they had to develop and test an entirely new medication.
The Latest on: Amiloride
via Google News
The Latest on: Amiloride
- Bartter Syndrome Treatment Market Professional Survey Report 2018 on February 14, 2019 at 10:27 pm
Some patients may require medications such as potassium-sparing diuretics such as spironolactone or amiloride. Growth hormone therapy is also considered as a successful Bartter syndrome treatment. Bar... […]
- Hydrochlorothiazide-amiloride versus hydrochlorothiazide alone for essential hypertension: effects on blood pressure and serum potassium level on September 27, 2018 at 10:14 pm
In a double-blind randomized controlled trial the effects on the blood pressure and the serum potassium concentration of hydrochlorothiazide-amiloride hydrochloride (Moduret) and hydrochlorothiazide a... […]
- Amiloride potentiates the vascular effects of atrial natriuretic factor on October 3, 2017 at 5:00 pm
We have demonstrated an interaction between the effects of amiloride and atrial natriuretic factor (ANF) on the vascular system. In precontracted rabbit aortic strips the relaxant effect of a combinat... […]
- How to Take Metformin on September 29, 2017 at 5:00 pm
How to Take Metformin. Diabetes is a very common disease that affects ... Inform your doctor if you have been taking or currently take furosemide, nifedipine, cimetidine, ranitidine, amiloride, triamt... […]
- Amiloride / Hydrochlorothiazide Sales, Price Analysis, & Sales Forecasts 2016-2021 - Research and Markets on July 17, 2017 at 1:56 am
DUBLIN--(BUSINESS WIRE)--The "Amiloride / Hydrochlorothiazide Sales, Price Analysis, & Sales Forecast - 2017" report has been added to Research and Markets' offering. Find out the sales of Amiloride / ... […]
- Amiloride directly inhibits the Na,K-ATPase activity of rabbit kidney proximal tubules on July 14, 2016 at 9:19 pm
Amiloride inhibited the ouabain-sensitive rate of oxygen consumption (QO2) of a suspension of rabbit intact proximal tubules in the presence of different concentrations of extracellular sodium. Measur... […]
- Salt taste transduction occurs through an amiloride-sensitive sodium transport pathway on June 5, 2016 at 1:23 am
The inward current caused by sodium chloride placed on the mucosal surface of an in vitro preparation of rat dorsal lingual epithelium can be substantially reduced by the blocker of sodium ion transpo... […]
- Methyl isobutyl amiloride delays normalization of brain intracellular pH after cardiac arrest in rats on September 24, 2014 at 4:59 pm
Objective: The sodium/hydrogen ion (Na sup +/H sup +) antiporter system of brain cells is responsible for reducing intracellular acid loads and regulating cellular volume. Activation of this system du... […]
- Photosensitive version of amiloride allows regulating the function of sodium-specific ion channels with light on July 21, 2014 at 5:00 pm
The diuretic agent amiloride is used for the treatment of high blood pressure. Ludwig Maximilian University of Munich researchers have now synthesized a photosensitive version, which allows regulating ... […]
- Polymorphisms of Amiloride-Sensitive Sodium Channel Subunits in Five Sporadic Cases of Pseudohypoaldosteronism: Do They Have Pathologic Potential? on April 21, 2011 at 5:00 pm
Address all correspondence and requests for reprints to: Keiko Arai, M.D., Department of Physiology, Nippon Medical School, 1–1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan. E-mail: arai_keiko/[email protected] […]
via Bing News