Summary: The study identifies new drugs that can help treat depression and anxiety disorders without many of the side effects of other drugs currently being evaluated.

Source: Medical University of Vienna

A variety of medications are now available to treat mental illnesses—such as depression and anxiety disorders. However, although these drugs provide benefits, they are associated with side effects.

Consequently, medical researchers constantly strive to improve the pharmacological properties of therapeutic agents to optimize the benefit-to-side-effect ratio. A research group led by Harald Sitt at MedUni Vienna’s Center for Physiology and Pharmacology conducted research to identify new drugs that could be used in the treatment of neuropsychiatric disorders.

Importantly, lead compounds show reduced rates of drug abuse and other adverse effects compared to other agents currently under evaluation.

The research results were recently published in the journal Molecular psychiatry.

In their preclinical trials, a research team led by Harald Sitt of the Institute of Pharmacology at the Center for Physiology and Pharmacology of MedUni Vienna identified the potential of certain substances from the synthetic cathinone family of compounds to treat mental illness.

Cathinones are derived from cathine found in the khat plant and are known to release monoamines such as noradrenaline, dopamine and serotonin.

“These substances first showed a serotonin-related effect in our cell models, then in our mouse model,” says Harald Sitt, referring to this messenger substance as a key factor in the treatment of depression and anxiety disorders such as social phobia or post-traumatic stress disorder.

The cathinone compounds used in the study attracted scientists’ attention because of their selective release of serotonin without significantly increasing dopamine levels in the brain’s “reward center.”

“Consequently, the new drugs we are investigating are less likely to be abused and are generally associated with fewer side effects,” emphasizes Harald Sitt.

Serotonin is released with less stress

Mental illnesses such as depression and anxiety disorders can be alleviated by increasing the level of cellular serotonin in the brain. This is often achieved by substances classified as antidepressants.

The mechanism of action of these selective serotonin reuptake inhibitors (SSRIs) is based on blocking the reuptake of serotonin from the synaptic cleft (neural interspace), which increases the level of serotonin in the intracellular compartment.

This shows a distressed woman looking out the window.
Mental illnesses such as depression and anxiety disorders can be alleviated by increasing the level of cellular serotonin in the brain. The image is in the public domain.

Note, “classical” antidepressants prevent and “block” the serotonin transporter.

In contrast, recent data from preclinical and clinical studies have identified the potential of drugs that induce the release of serotonin via the serotonin transporter, i.e., substances that reverse the natural transport pathway of the serotonin transporter.

However, the serotonin-releasing agents currently undergoing clinical trials carry abuse and harmful side effects. Like MDMA, also known as “ecstasy”, it is taken as a “party drug” in non-clinical settings.

“Our study identifies the first representatives of a new class of serotonin-releasing drugs and does not cause various adverse effects,” said the leader of the study, Harald Sitt. ) and Marco Nilo (Center for Physiology and Pharmacology at MedUni Vienna) in collaboration with the Vienna University of Technology, Florida Atlantic University, Peking University and the National Institute on Drug Abuse in Baltimore.

watch out

This shows the appearance of the two heads and the brain in the light bulb

So psychopharmacology research news

Author: Karin Kirschbichler
Source: Medical University of Vienna
Contact: Karin Kirchbichler – Medical University of Vienna
Image: The image is in the public domain.

Preliminary study: Open Access.
Serotonin-releasing agents reduce off-target effects” by Harald Sith et al Molecular psychiatry


Draft

Serotonin-releasing agents reduce off-target effects

Increasing levels of serotonin (5-HT) in the brain improves symptoms of depression and anxiety-related disorders such as social phobia and post-traumatic stress disorder.

Recent evidence from preclinical and clinical studies has confirmed the therapeutic potential of drugs that induce the release of 5-HT via the 5-HT-transporter. However, the current 5-HT release compounds under clinical investigation are subject to abuse and harmful side effects.

Here, we show that S-Enantiomers of some ring-substituted cathinones show selectivity to release 5-HT ex vivo and in vivo and produce 5-HT-related effects in preclinical behavioral models.

Importantly, lead cathinone compounds (1) do not induce significant dopamine release and (2) exhibit off-target activities on vesicular monoamine transporters and 5-HT.2 bLow abuse-responsibility and low potential for adverse events.

Taken together, our findings identify these agents as lead compounds that may be useful in the treatment of diseases where 5-HT elevation is beneficial.

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