February 14, 2007

First Antipsychotic Targeting GABA to Enter Phase II Trials

BioLineRx Ltd. (Israel) announced that its novel antipsychotic for schizophrenia, so far simply named "BL-1020", has passed Phase I clinical trials and is expected to enter phase II trials later this year.

According to BioLineRx, BL-1020 - the first GABA enhancing antipsychotic for the treatment of schizophrenia - is "designed to simultaneously target the dopamine hyperactivity and GABA hypoactivity of schizophrenia" and "BL-1020 was well tolerated and showed an improved safety profile reducing extrapyramidal symptoms that are experienced with currently available therapies."

GABA, which stands for Gamma-aminobutyric acid, is a neurotransmitter in the brain and central nervous system (CNS).

The company hopes that increased GABA activity might also reduce anxiety and improve cognitive function in patients suffering from schizophrenia.

Professor Michael Davidson, Director Department of Psychiatry, Sheba Medical Center commented,

"Results from the Phase I trial indicate that BL-1020 might be better tolerated than currently available drugs. In addition BL-1020 is the only antipsychotic with the potential to increase the activity of the neurotransmitter GABA which appears to be deficient in schizophrenia. Increased GABA activity might also reduce anxiety and improve cognitive function in patients suffering from schizophrenia."

The Phase I trial of BL-1020 was a randomized, double blind, placebo-controlled, dose-escalation, single center study in healthy adult males (ages 21-45). The primary objective was to evaluate the safety and tolerability of escalating doses of BL-1020. The secondary objectives were to determine the pharmacokinetics of BL-1020, and to assess its ability to block activity of the neurotransmitter dopamine, implicated in schizophrenia.

Their results indicate that BL-1020 is protective against extrapyramidal symptoms (EPS) and that it also acts as a GABA enhancer by delivering GABA to the central nervous system (passing into the brain through the blood-brain barrier which simply administering GABA cannot do).

Source: BioLineRx Successfully Completes Phase 1 Clinical Trials of BL-1020, First in Class GABA-Enhanced Antipsychotic for the Treatment of Schizophrenia

Additional Reading:
GABA Cells in Schizophrenia and Bipolar Disorder
Working memory: a new target?
Brain chemistry and prevention


This sounds like one of the more promising drugs in development. Hopefully it will have a low effect on histamines. Maybe slight serotonin antagonism could be helpful as well. I would imagine that by increasing GABA and blocking dopamine that it would be very sedating. Almost like GHB or Ambien. But only time will tell.

Just last week I had a really bad reaction to Geodon and went to the hospital thinking I was having a heart attack. That's scary stuff...

Posted by: Cory Schulz at February 14, 2007 10:27 AM

Actually, the more I read about it, the more promising it sounds.


It seems that it is not overly sedating and does have some activity on serotonin receptors. If it increases prolactin too much that could cause certain side effects... but everything else looks promising.

There seems to be quite a variety of new drugs being developed, and many of them seem to be focusing more on the negative and cognitive symptoms. I think that within the next 5 to 10 years we will see many new classes of drugs develop. Hopefully sooner then later.

Posted by: Cory Schulz at February 14, 2007 10:41 AM

There are or will be a wide variety of drugs for schizophrenia. On the face of it this should be a good thing, but when a drug is taken the body adapts to the blocking effect of the drug by growing extra receptors (upregulation) this is not too much of a problem if you remain on the said drug but if you wanted to come of all medication you may develop supersensitivity psychosis, when maybe you only had a minor need for antipsychotics.
However my point is that if you need to change between greatly different medications because they are not working the variations in receptor profiles exposed to upregulation in the first drug may not be catered for in the second drug leaving you possibly more ill and there being less likelyhood of total withdrawl of medication.
Perhaps 'goldlocks' meds such as aripiprazole and bifprunox do not cause uprgulation, meaning they could be used as a last stage in treatment prior to carefully monitored withdrawl as they may downregulate but a problem being this would only apply to dopamine and a few other receptors. Hope this is interesting for you.

Posted by: Matt at February 14, 2007 03:32 PM

Yeah, when changing meds there is always a transition period where the cells have to readapt their receptor sensitivity. But I would think that with the extreme amounts of dopamine being released in schizophrenia, that the receptors would naturally lower their quantity and sensitivity. Maybe this is part of the problem in schizophrenia, is the inability of the receptors to properly regulate themselves in this way. I would not be surprised. But that would imply that there is an entire malfunction in the genetic and protein mechanism of the neurons. And that's possibly something that just isn't curable...
The partial dopamine agonists very much interest me. Their novel ways of action are something I never thought possible. But when I took Abilify I noticed that everything seemed really boring and not enjoyable. They neutralize dopamine almost too well. We still need a little burst of dopamine every once in a while so we know that something exciting happened and that we're still alive.

Posted by: Cory Schulz at February 14, 2007 04:49 PM

Hi, I suffer from a psychosis-tendency since 16 years now. It was a horror-trip taking the old neurolepic drugs ( Haldol, Lyogen, Fluanxol etc.. ) when there were no second generation drugs available in the 90´s. Today I feel quite ok taking a little Amisulpride ( e.g. SOLIAN ): It is Heaven compared to the first generation drugs. Maybe that the new drug tested in Israel is promising - given that the role of GABA in schizophrenia is really understood today. But anyway I am in favour for all scientists who try to help us poor people with mental disorders ! We have a really devastating desease in terms of social life etc..
Aripiprazol caused a severe heartache and arhythmics which made me go to a hospital as emergency case.
Nothing special was found, but the heartache is still there today, though I canceled taking Abilify a long time ago now.
That is a personal side-effect, certainly aripiprazol has helped some people to get out of the dull condition often caused by a psychosis.

Posted by: Kevin at February 24, 2007 01:33 PM

My name is Adolfo Cohen and I have a brother who suffers from Schizophrenia I heard the new Trials with BL-1020 (Bioline RX LTD) I live in Telaviv Israel. I would like to be in touch with the center that is doing the trial for the condition of my brother. Thanks a lot.

Posted by: Adolfo Cohen at February 27, 2007 01:44 PM

BioLineRx expects to initiate its "Phase II maximal tolerated dose clinical trial" for BL-1020 in the end of June, 2007. The Phase II trial sites selected are in Romania and Israel.


Posted by: Jeanie at May 17, 2007 11:52 AM

At last.

I would like to be part, of a clinical trial, so I can have this drug now.

I have Faith in this one.


Posted by: Peter at June 6, 2007 04:36 PM

is first stage of Schizophrenia is cureable ?

Posted by: arun at July 13, 2007 12:01 AM

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