Research team developing BU10119, led by Sarah Bailey, front-center, and Stephen Husbands, back (University of Bath)
7 November 2017. A new type of treatment for depression that works differently from most other anti-depressive drugs was shown in lab mice to reduce depression-like behaviors. Results of the study by a team from University of Bath in the U.K. appear in yesterday’s issue of the British Journal of Pharmacology (paid subscription required).
Depression is a common mood disorder, but can become a serious and disabling condition, when it persists for long periods or interferes with day-to-day living. World Health Organization estimates 300 million people worldwide suffer from depression. Centers for Disease Control and Prevention says depression affects about 7.6 percent of the U.S. population age 12 and over in any 2-week period.
The most common drugs prescribed for depression are called selective serotonin reuptake inhibitors, or SSRIs, that help increase the supply of serotonin in the brain. Serotonin is a neurotransmitter, a chemical emitted by nerve cells. SSRIs prevent brain cells from reabsorbing serotonin, thus making more of the substance available. SSRIs are also prescribed to treat anxiety disorders.
SSRIs are considered safe and cause few side effects, but are often not effective in as many as half of individuals with depression. The Bath team from the labs of pharmacologist Sarah Bailey and medicinal chemist Stephen Husbands are developing an alternative drug code-named BU10119 that works on kappa opioid receptors, proteins in the brain associated with addiction and depression. The current opioid emergency in the U.S. and elsewhere highlights the addictive nature of these proteins, but similar receptors are implicated with depression as well.
BU10119 is a combination of two established drugs to treat addiction, buprenorphine and naltrexone, that block the actions of kappa opioid receptors. The new study, say the authors, is the first test of these compounds combined into a single drug on lab animals. In these tests, the researchers devised tasks for the mice to perform where certain reactions by the mice would indicate evidence of depression. One test, for example, involved forcing mice to swim, where longer times that the mice remained immobile in the water are an indicator of depression.
The results show mice given BU10119 were less likely to exhibit depression-like behaviors in tests of mobility, activity, eating, and pain reception than similar mice given a placebo. In other tests, the Bath team pre-treated the mice with BU10119, which were less likely to exhibit insensitivity to pain induced from stress. In these cases, the BU10119 was given 2 hours before a single induced stress experience, as well as 3 doses every 2 hours to prevent stress from repeated experiences.
BU10119 is one of several compounds from Bath licensed to biotechnology company Orexigen Therapeutics in San Diego for commercial development. “This research builds on our previous work which showed that combining buprenorphine and naltrexone can give antidepressant effects in mice,” says Husbands in a university statement. “By combining the effects of both drugs in one molecule we hope that a safe and effective drug will eventually be the outcome.”
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