New substances that activate adrenalin receptors instead of opioid receptors have a similar pain relieving effect to opiates, but without the negative aspects such as respiratory depression and addiction. This is the result of research carried out by an international team of researchers led by the Chair of Pharmaceutical Chemistry at Germany’s Friedrich-Alexander-University (FAU). Their findings, have now been published in the journal Science.
Opioids are said to be a blessing for patients suffering from severe pain, but they also have serious side effects: morphine, can cause nausea, dizziness and constipation and can also often cause slowed breathing that can even result in respiratory failure. In addition, opiates are addictive – a high percentage of the drug problem in the USA is caused by pain medication, for example.
In order to tackle the unwanted medical and social effects of opioids, researchers all over the world are searching for alternative analgesics. Prof. Dr. Peter Gmeiner, Chair of Pharmaceutical Chemistry at FAU is one of the researchers currently following a lead that seems very promising: “Many non-opioid receptors are involved in pain processing, but only a small number of these alternatives have as yet been validated for use in therapies”, he explains. Gmeiner and a team of researchers from Erlangen, China, Canada and the USA have now turned their attention to a new receptor that is responsible for binding adrenaline – the alpha 2A adrenergic receptor. There are already some analgesics that target this receptor such as brimonidine, clonidine and dexmedetomidine. Gmeiner: “Dexmedetomidine relieves pain, but has a strong sedative effect, which means its use is restricted to intensive care in hospital settings and is not suitable for broader patient groups.”
The aim of the research consortium is to find a chemical compound that activates the receptor in the central nervous system without a sedative effect. In a virtual library of more than 300 million different and easily accessible molecules, the researchers looked for compounds that physically match the receptor but are not chemically related to known medication. After a series of complex virtual docking simulations, around 50 molecules were selected for synthesis and testing and two of these fulfilled the desired criteria. They had good bonding characteristics, activated only certain protein sub-types and thus a very selective set of cellular signal pathways, whereas dexmedetomidine responds to a significantly wider range of proteins.
The successful separation of analgesic properties and sedation is a milestone in the development of non-opioid pain medication, especially as the newly-identified agonists are comparatively easy to manufacture and administer orally to patients. However, Prof. Gmeiner has to dampen any hopes of rapid widespread use in human medicine: “We are currently still talking about basic research. The development of medication is subject to strict controls and in addition to significant amounts of funding, it takes a long time. However, these results still make us very optimistic.” (https://www.science.org/doi/10.1126/science.abn7065)
AR Issue #61
The Supernatural World of Graham Hancock
by Glen Kreisberg
