New knowledge on the pharmacology of dopamine stabilizers

February 24, 2012, Karolinska Institutet

A study from Karolinska Institutet in Sweden shows that a new drug for Huntington's disease – pridopidine or dopamine stabiliser ACR16 – might operate via previously unknown mechanisms of action. Researchers have found that at very low concentrations, ACR16 binds to the sigma-1 receptor, a protein in the brain important to neuronal function and survival. This new knowledge can be used to develop future treatments for schizophrenia, involuntary Parkinsonian tremors and neurodegenerative diseases.

"It's conceivable that some of the beneficial effects of dopamine stabilisers are mediated via the sigma-1 receptor," says principal investigator Daniel Marcellino of the Department of Neuroscience. "Our results suggest a formerly overlooked aspect of dopamine stabiliser pharmacology."

Dopamine stabilisers are a new class of drug substance originally developed by Swedish Nobel laureate Professor Arvid Carlsson. In clinical trials, these substances have revealed promising results against neurological and neuropsychiatric conditions that currently lack suitable treatment, such as schizophrenia and the dyskinesia (involuntary tremors) caused as an adverse effect of Parkinson's drugs.

Pridopidine or dopamine stabiliser ACR16 (also known as Huntexil), is in an advanced phase of clinical trials (phase III) for the relief of the motor symptoms of , an incurable disease caused by neuronal degeneration in certain parts of the brain. The disease, which is hereditary, is characterised by motor and subsequent psychiatric disorders, leading to a protracted death. There is currently only one drug registered for the relief of Huntington's symptoms, but as it has several adverse effects there is a strong demand for alternative treatment options.

Dopamine stabilisers are thought to exert their beneficial effects primarily via the dopamine D2 receptor, which is a well-known site of action for drugs for Parkinson's disease and schizophrenia. However, in a study published recently in the scientific journal Molecular Psychiatry, researchers at Karolinska Institutet have shown that ACR16 and another stabiliser (-)-OSU6162 also bind to the sigma-1 receptor in low concentrations.

"We found that ACR16 binds to the sigma-1 receptor at concentrations 100 times lower than those reported for interaction with the D2 receptor," says Dr Marcellino. "This is extremely interesting since experimental studies have shown that sigma-1 receptor ligands have positive effects in schizophrenia and protect against cell death in neurodegenerative conditions."

Explore further: New drug seems well-tolerated and merits further investigation in patients with Huntington's disease

More information: "The dopamine stabilizers ACR16 and (−)-OSU6162 display nanomolar affinities at the σ-1 receptor" K Sahlholm, P Århem, K Fuxe & D Marcellino,, Molecular Psychiatry advance online publication 21 February 2012; doi: 10.1038/mp.2012.3

Related Stories

New drug seems well-tolerated and merits further investigation in patients with Huntington's disease

November 7, 2011
A novel drug (pridopidine) that stabilises dopamine signalling in areas of the brain that control movement and coordination, appears well tolerated and warrants further study in patients with Huntington's disease (HD), a ...

Receptor limits the rewarding effects of food and cocaine

July 12, 2011
(Medical Xpress) -- Researchers have long known that dopamine, a brain chemical that plays important roles in the control of normal movement, and in pleasure, reward and motivation, also plays a central role in substance ...

Recommended for you

Intensive behavior therapy no better than conventional support in treating teenagers with antisocial behavior

January 19, 2018
Research led by UCL has found that intensive and costly multisystemic therapy is no better than conventional therapy in treating teenagers with moderate to severe antisocial behaviour.

Babies' babbling betters brains, language

January 18, 2018
Babies are adept at getting what they need - including an education. New research shows that babies organize mothers' verbal responses, which promotes more effective language instruction, and infant babbling is the key.

College branding makes beer more salient to underage students

January 18, 2018
In recent years, major beer companies have tried to capitalize on the salience of students' university affiliations, unveiling marketing campaigns and products—such as "fan cans," store displays, and billboard ads—that ...

Inherited IQ can increase in early childhood

January 18, 2018
When it comes to intelligence, environment and education matter – more than we think.

Baby brains help infants figure it out before they try it out

January 17, 2018
Babies often amaze their parents when they seemingly learn new skills overnight—how to walk, for example. But their brains were probably prepping for those tasks long before their first steps occurred, according to researchers.

Reducing sessions of trauma-focused psychotherapy does not affect effectiveness

January 17, 2018
Posttraumatic Stress Disorder (PTSD) patients treated with as few as five sessions of trauma-focused psychotherapy find it equally effective as receiving 12 sessions.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.