Potential New Lead Compounds for the Treatment of Depression and Anxiety Disorders

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Overview: Study identifies potential new drugs that could help treat depression and anxiety without many of the adverse effects of other drugs currently being evaluated.

Source: Medical University of Vienna

Currently, several types of medications are available for the treatment of mental illnesses, such as depression and anxiety disorders. While these drugs offer benefits, they also come with adverse side effects.

As a result, medical researchers are constantly striving to improve the pharmacological properties of therapeutic agents to optimize the ratio of benefits to side effects. The research group led by Harald Sitte from the Center for Physiology and Pharmacology at MedUni Vienna has conducted a study to identify new drugs that could potentially be used to treat neuropsychiatric disorders.

Importantly, the lead compounds showed a reduced risk 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 experiments, the research team, led by Harald Sitte of the Institute of Pharmacology at MedUni Vienna’s Center for Physiology and Pharmacology, identified the potential of certain substances from the family of synthetic cathinone compounds for the treatment of mental illness.

Cathinones are derived from cathine, which is found in the khat plant, and are known for their ability to release monoamines such as norepinephrine, dopamine, and serotonin.

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

The cathinone compounds used in the study caught the scientists’ attention because of their preference for releasing serotonin without significantly increasing dopamine levels in the brain’s “reward center.”

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

Serotonin release with less risk

Mental health conditions such as depression and anxiety disorders can be alleviated by increasing extracellular serotonin levels in the brain. This is usually achieved by substances classified as antidepressants.

The mechanism of action of these so-called selective serotonin reuptake inhibitors (SSRIs) is based on blocking the reuptake of serotonin from the synaptic cleft (neuronal space), thereby increasing the amount of serotonin in the extracellular space.

Mental health conditions such as depression and anxiety disorders can be alleviated by increasing extracellular serotonin levels in the brain. The image is in the public domain

Note that “classical” antidepressants inhibit and “block” the serotonin transporter.

In contrast, recent evidence from preclinical and clinical studies has shown the potential of drugs that induce the release of serotonin via the serotonin transporter, ie substances that reverse the natural direction of transport of the serotonin transporter.

However, the serotonin-releasing agents currently undergoing clinical trials carry the risk of abuse and harmful side effects such as MDMA, also known as ‘ecstasy’, which is used in non-clinical situations as a ‘party drug’.

“Our study identified the first representatives of a new serotonin-releasing class of drugs that do not cause various adverse effects,” said study leader Harald Sitte, summarizing the results of the study, which was conducted by first author Felix Mayer (Florida Atlantic). University ) and Marco Niello (Center for Physiology and Pharmacology at MedUni Vienna) in collaboration with Vienna University of Technology, Florida Atlantic University, Peking University and the National Institute of Drug Abuse in Baltimore.

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About this psychopharmacology research news

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

Original research: Open access.
“Serotonin-Releasing Agents with Reduced Off-Target Effects” by Harald Sitte et al. Molecular Psychiatry


Abstract

Serotonin-releasing agents with reduced off-target effects

Increasing extracellular levels of serotonin (5-HT) in the brain alleviate the symptoms of depression and anxiety-related disorders, for example, social phobia and post-traumatic stress disorder.

Recent evidence from preclinical and clinical studies has demonstrated the therapeutic potential of drugs that induce the release of 5-HT via the 5-HT transporter. Nevertheless, the current 5-HT-releasing compounds currently under clinical investigation carry the risk of abuse and harmful side effects.

Here we show that Senantiomers of certain ring-substituted cathinones show a preference for the release of 5-HT ex vivo and in vivo, and exert 5-HT associated effects in preclinical behavioral models.

Importantly, the lead cathinone compounds (1) do not induce substantial dopamine release and (2) show reduced off-target activity at vesicular monoamine transporters and 5-HT2Breceptors, indicative of a low potential for abuse and a low potential for side effects.

Taken together, our findings identify these agents as lead compounds that may prove useful for the treatment of conditions where elevation of 5-HT has been shown to be beneficial.

The Valley Voice
The Valley Voicehttp://thevalleyvoice.org
Christopher Brito is a social media producer and trending writer for The Valley Voice, with a focus on sports and stories related to race and culture.

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