Inside the Mind

A story of science, progress & mental health

‘Like penicillin for psychiatric illness’: this is how science will remember the discovery of chlorpromazine: the first psychiatric drug developed in 1950.
Chlorpromazine was indeed a landmark discovery. Within a few short years, other medications for conditions like depression, psychosis and anxiety would become available, reshaping the way that clinicians and society approached mental illness. But the new drugs were far from a panacea.
The first-wave of psychiatric medications were largely produced by trial and error. Scientists would alter the chemical configuration of the drugs and analyse the effects on patients.
And this approach worked – some of the drugs developed in this way are still in use today. But there were drawbacks. The medications successfully adapted the neurobiological processes that caused problems but, because they weren’t perfectly targeted, they affected other processes as well. Hence, side effects.
People taking medication often experience side effects that range from the annoying to the severe. In some cases, this is enough to make individuals who could benefit from medication avoid it altogether. Side effects are a longstanding issue with psychiatric medication. But we are becoming better equipped to address the problem.
The advent of SSRIs in the 1990s heralded the first wave of ‘rationally designed’ antidepressants. Unlike the ‘trial and error’ psychiatric medications that came before them, SSRIs were specifically designed to interact with the neurotransmitter serotonin, leading to fewer adverse effects and more effective treatment.
SSRIs are generally well tolerated, but they aren’t perfect. If we want to reduce side-effects and increase effectiveness even further, we need to improve our understanding of how the neurobiological components involved in psychiatric illness behave and are structured on the atomic and molecular level.
Thanks to ongoing advances in technology, we’re now better equipped than ever to explore the nanoscale processes behind mental health, paving the way for more targeted, more effective treatments.
 Diamond's microfocus beamline, I24, where the work took place
Recent work from the clinical-stage company, Heptares Therapeutics, has helped to illuminate several clear biological targets implicated in neurological disorders such as schizophrenia, Alzheimer’s disease and addiction. And like the introduction of chlorpromazine and SSRIs before it, these discoveries could prove a landmark moment in the development of psychiatric medication.
Around 30% of drugs on the market currently target a component of the cell known as ‘GPCRs’: protein receptors that sit in the membrane surrounding our cells and carry messages into and between cells. GCPRs are vital to an array of biological functions and are the largest and most important family of drug targets currently in existence.
Using Diamond’s Microfocus Macromolecular Crystallography beamline (I24), scientists from Heptares have been able, for the first time, to study the structure of GPCR receptors located in the brain that affect mood, learning and behaviour.
And the research didn’t just unravel the atomic structure of these receptors; as Fiona Marshall, Chief Scientific Officer at Heptares, explains: “It also enabled our scientists to see inside the receptors in minute detail and to use this information to design potential drug molecules that fit perfectly with the receptors to modulate their effects.”
This research provides a powerful new approach for the design of psychiatric medication, and for a range of other diseases.
Because if we can develop a drug molecule that fits perfectly – like the key to a lock – inside these receptors, then we could see the next generation of enhanced psychiatric medications offering significantly reduced side-effects.
It’s clear that improved medication alone will not remedy all of the complex issues associated with psychiatric illness. And there’s still much work to do before we can fully understand and address the biomedical, psychological and environmental factors that cause one in four of us to suffer with mental illness in the UK every year.
But, along with pioneering fields such as stem cell research and personalised medicine, advanced rational drug design will have a vital role to play.
As we uncover more about the nanoscale structures and processes behind mental health, we’re moving closer to drugs that work better and trigger fewer side effects. And this is really good news.
Science doesn’t have all of the answers, but by understanding the molecular mechanisms that contribute to mental health issues, we will help to improve lives. There’s no magic fix when it comes to mental illness, but research does a have meaningful impact: practical tools, tangible progress and hope.

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