Researchers from the School of Pharmacy and Pharmacology at Bath University (U.K.) have developed a drug which shows signs of treating depression and anxiety through a previously uncharted mechanism. The drug (BU10119) is composed of two compounds, a buprenorphine analogue and naltrexone.
The research group used oral dosage of BU10119 in mice and tested the mice for behavioural symptoms related to depression and anxiety. Mice treated with the drug exhibited behaviours associated with a reduction in anxiety and depression without any side effects to motor function or signs of reward pathway over activation.
In addition, the administration of BU10119 blocked stress induced analgesia – a pain suppression response induced by stress or fear – exhibiting the potential use of the drug for treating anxiety and depression.
Buprenorphine interacts with opioid receptors, working through the same mechanism as morphine and other opiate alkaloids. Naltrexone is introduced to the drug to increase the safety of the compound by negating some of the negative side effects which make opiate alkaloids commonly used drugs of abuse.
Recent trends in antidepressant therapies have indicated that targeting opioid receptors may offer a novel mechanism for treating depression and anxiety.
In response to stress, opioids are released in the brain resulting in an activation of certain receptors in the brain (kappa-receptors), which elicits depressive behaviours. This kappa-receptor is what is blocked by buprenorphine to produce the antidepressant and antianxiety behaviour seen in the mouse experiments shown by researchers.
The most commonly prescribed class of antidepressants are selective serotonin reuptake inhibitors (SSRIs) which block the action of a protein which removes serotonin from where it acts on the neurons. Serotonin is targeted in depression and anxiety drugs as it is a neurotransmitter which is directly correlated to mood and is reduced in the brains of people with depression.
Although SSRI drugs have been very effective they are only effective in treating 50% of people with depression, highlighting the need for additional antidepressant medications.
Potential Future BU10119 Benefits
By combining buprenorphine with naltrexone to create a BU10119 it’s possible to selectively benefit from the kappa-receptor blocking without negative effects associated with opiate alkaloids. The drug will need to go through further pre-clinical testing in animal models before being tested in humans.
But hopefully this drug could be used to treat depression and anxiety, while improving the mental health outcome for the 50% of people with depression and anxiety who don’t respond to SSRIs.
Depression and anxiety are mental health issues which can be extremely debilitating and can also lead to fatalities. The authors of this research state their hope that this drug can be developed into a clinical therapeutic so that the burden of depression and anxiety for those without current treatment options can potentially be relieved with BU10119 or a similar kappa-receptor blocker.
Abdulrahman Almatroudi, Mehrnoosh Ostovar, Christopher P Bailey, Stephen M Husbands, Sarah J Bailey Antidepressant-like effects of BU10119, a novel buprenorphine analogue with mixed κ/μ receptor antagonist properties, in mice British Journal of Pharmacology. 6 November 2017: DOI: 10.1111/bph.14060
Author: Geoffrey Potjewyd; Regenerative Medicine & Neuroscience PhD student at the University of Manchester.