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Brain makes its own version of Valium

Researchers at Stanford University School of Medicine have found that a naturally occurring protein secreted only in individual regions of the mammalian brain can act as a kind of Valium to certain types of seizures.

Natural Valium for the treatment of many mental illnesses

The protein is known as the diazepam binding inhibitor, or DBI. It calms the rhythm of an important brain circuit and thus can be valuable in developing new therapies with fewer side effects. It is said to be effective not only for treating epilepsy but possibly also for anxiety disorders en sleep problems.

"This is one of the most exciting findings we've had in many years," said John Huguenard, PhD John Huguenard, professor of neurology and neurological sciences and the lead author of the study. “Our results show for the first time that a nucleus deep in the center of the brain generates a small protein product, or peptide, that works just like benzodiazepines. This class of drugs includes not only the anti-anxiety drug Valium (generic name diazepam), which was first marketed in 1965, but also its predecessor Librium, which was discovered in 1955, and the more recently developed hypnotic drug Halcyon.

Known for being addictive and so prone to abuse, valium used to be used as a treatment for epilepsy. There have been newer, better ones over time anti-epileptic drugs come.

The effect of natural Valium

For decades, DBI has also been known to researchers under a different name: ACBP. In fact, it is found in every cell of the body, where it is an intracellular transporter of a metabolite called acyl-CoA. "But in a very specific and very important brain circuit that we have been studying for many years, DBI not only leaves the cells that made it, but is - or undergoes further processing into - a natural anti-epileptic compound," said Huguenard. “In this circuit, DBI or one of the peptide fragments of DBI acts as a biochemical Valium and produces the same neurological effect.

Other endogenous (internally produced) substances have demonstrably effects that are comparable to those of psychoactive medicines. In 1974, endogenous proteins called endorphins with biochemical activity and analgesic properties similar to those of opiates were isolated. A more recent series of substances, the endocannabinoids, mimic the memory, appetite and analgesic effects of the psychoactive compounds of cannabis, or marijuana.

Drugs such as benzodiazepines enhance GABA-induced inhibition. That changes the shape of the receptor, making it hyper responsive to GABA. These receptors come in many different types and subtypes, and not all of them respond to benzodiazepines. DBI binds to the same site where benzodiazepines bind to benzodiazepines on benzodiazepine resistant GABA receptors. What that means so far has remained unclear.

Huguenard, Christian and their colleagues also showed that DBI has the same inhibition - enhancing effect on nerve cells in an adjacent thalamic region - but also that, importantly, no DBI is produced naturally in or near this region; in the corticothalamic circuit, at least, DBI appears to be released only in the thalamic reticular nucleus. Thus, the action of DBI on GABA receptors appears to be well controlled only in specific brain areas.

Natural Valium can potentially end epilepsy

Hugenard does not yet know whether it is DBI on its own, or one of the peptide fragments (and if so which ones), that performs the active inhibitory role. But, he said, by finding out exactly which cells release DBI under which biochemical conditions, it may one day be possible to develop agents that can jump in seizure onset and boost their activity in epileptic patients. , effectively nipping them in the bud.

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