AboutDr. Ravindra Bhaskar Ghooi Expertise I can provide information on drugs and medicines, their actions, uses, interactions and adverse effects. To avoid confusion, generic names of
medicines may please be provided. I am a pharmacologist, having worked
on animal and human pharmacology, and presently I am the Dean of Bilcare Research Academy, where we teach courses on clinical research. We dont work on saturdays and sundays, hence questions reachng me on these days will be replied on Monday, please bear with me.
Question QUESTION: Dr. Ravi - has Antalarmin been cleared for human use yet? If so, what form is it prescribed in, and how is the dosage rate set? I'm a physiology student, developing a mock research project, that I would like to use Antalarmin for.
Thanks,
Donna
ANSWER: Hi Donna,
Antalarmin is a prototype CRF antagonist. There are quite a number of newer antagonists which are being considered for clinical work. Chronic antalarmin treatment also showed antiinflammatory effects and has been suggested as having potential uses in the treatment of inflammatory conditions such as arthritis, as well as stress-induced gastrointestinal ulcers and irritable bowel syndrome.However neither antalarmin or its congeners have been marketed anywhere in the world.
Regards
Ravi Ghooi
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QUESTION: Thanks, Dr. Ravi - Why hasn't antalarmin/equivalents been marketed yet? Are there any approved CRH antagonists available for use?
ANSWER: Hi Donna,
No Antalarmin has not yet been marketed anywhere in the world. So also there are no other CRF antagonists in clinical use. Let me quote an authoritative article on CRF antagonists:
"Experts outside the industry are more optimistic about antagonists of the corticotropin releasing factor (CRF), a stress hormone. The link between stress and depression is well-documented and there is evidence that levels of cortisol are elevated in the spinal fluid of depressed patients. "That's probably the best biology that's been worked out for depression," says Ranga Krishnan, chair of psychiatry at Duke University.
The only human trial of a CRF antagonist was a small but promising proof-of-principle study by Holsboer's group in Munich. But at high doses, the compound produced a troubling increase in liver enzymes, and was shelved when Belgium-based Janssen, which held the license, was acquired by Johnson and Johnson (J & J).
In 1996, Pfizer also abandoned a CRF antagonist when researchers there uncovered toxicity in preclinical studies. Still, both Holsboer and Pfizer maintain that the problems were specific to those compounds and have no bearing on the validity of the hypothesis. Nearly every major company is now pursuing CRF antagonists, which are widely acknowledged as the lead alternative to available antidepressants.
Most of the CRF compounds are in phase 1 trials or earlier. Because cortisol regulates immune response to infections, a successful CRF antagonist would have to act on the brain receptors but not in the periphery. "That's not an easy task," notes Krishnan. As a result, he says, "everyone is going very, very slowly and making sure they understand the pharmacology."
Unfortunately my personal opinion about Ranga Krishnan, whom I know is not very high. He is more of a pharmaceutical scientist than an academician, I really wont give much importance to his opinion. While we agree that stress-depression are linked I do not think that they have a cause and effect relationship, hence i for one do not have much hope from CRF antagonists as a therapeutic measure.
Ravi Ghooi
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QUESTION: Dr. Ravi - I truly appreciate the exchange with you! I was hopeful there might be a way to combine a CRF antagonist like Antalarmin with existing naltrexone and acamprosate to treat alcoholism. So my follow up question will tap into your creative side (I hope!). Is there something that can be compounded with naltrexone and acamprosate (maybe a neuropeptide Y) that might be helpful for those with AUD? Thanks again! Donna
Answer Hi Donna,
Ok now I understand what you are aiming at. During withdrawal there is a lot of stress and we know that during stress, release of corticotropin releasing factor takes place.
By usng antalarmin you are trying to block the action of CRF, there is yet another way of blocking CRF, not its action but its release.
CRF release can be blocked by a negative feedback mechanism through cortical hormones. Any corticosteroid blocks CRF release and hence using a steroid may help.
I would suggest you go through the stress hypothesis put forward by Hans Selye over 50 years ago.
Ravi Ghooi
