Corante

About this Author
DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

Chemistry and Drug Data: Drugbank
Emolecules
ChemSpider
Chempedia Lab
Synthetic Pages
Organic Chemistry Portal
PubChem
Not Voodoo
DailyMed
Druglib
Clinicaltrials.gov

Chemistry and Pharma Blogs:
Org Prep Daily
The Haystack
Kilomentor
A New Merck, Reviewed
Liberal Arts Chemistry
Electron Pusher
All Things Metathesis
C&E News Blogs
Chemiotics II
Chemical Space
Noel O'Blog
In Vivo Blog
Terra Sigilatta
BBSRC/Douglas Kell
ChemBark
Realizations in Biostatistics
Chemjobber
Pharmalot
ChemSpider Blog
Pharmagossip
Med-Chemist
Organic Chem - Education & Industry
Pharma Strategy Blog
No Name No Slogan
Practical Fragments
SimBioSys
The Curious Wavefunction
Natural Product Man
Fragment Literature
Chemistry World Blog
Synthetic Nature
Chemistry Blog
Synthesizing Ideas
Business|Bytes|Genes|Molecules
Eye on FDA
Chemical Forums
Depth-First
Symyx Blog
Sceptical Chymist
Lamentations on Chemistry
Computational Organic Chemistry
Mining Drugs
Henry Rzepa


Science Blogs and News:
Bad Science
The Loom
Uncertain Principles
Fierce Biotech
Blogs for Industry
Omics! Omics!
Young Female Scientist
Notional Slurry
Nobel Intent
SciTech Daily
Science Blog
FuturePundit
Aetiology
Gene Expression (I)
Gene Expression (II)
Sciencebase
Pharyngula
Adventures in Ethics and Science
Transterrestrial Musings
Slashdot Science
Cosmic Variance
Biology News Net


Medical Blogs
DB's Medical Rants
Science-Based Medicine
GruntDoc
Respectful Insolence
Diabetes Mine


Economics and Business
Marginal Revolution
The Volokh Conspiracy
Knowledge Problem


Politics / Current Events
Virginia Postrel
Instapundit
Belmont Club
Mickey Kaus


Belles Lettres
Uncouth Reflections
Arts and Letters Daily
In the Pipeline: Don't miss Derek Lowe's excellent commentary on drug discovery and the pharma industry in general at In the Pipeline

In the Pipeline

« Eli Lilly and Imclone: Sensible? Real? | Main | Day Off »

October 2, 2008

Taranabant Is No More

Email This Entry

Posted by Derek

Merck has taken a step that many people have been expecting, and announced that they are no longer developing taranabant, their cannabinoid antagonist (or is it an inverse agonist?)

I'd expressed grave doubts about the drug earlier this year, which turned out to be well-founded. That latter post included the line "I don't see how they can get this compound through the FDA", and now Merck seems to have come to the same conclusion. Further clinical data seem to have shown far too many psychiatric side effects (anxiety, depression, and so on), which increased along with the dose of the drug.

The cannabinoid antagonist field has already experienced a crisis of confidence after Sanofi-Aventis's rimonabant failed to gain approval in the US. This latest news should ensure that no company tries to develop one of these drugs until we've learned a great deal more about their pharmacology. Given how little we know about the mechanisms of these mental processes, though, that could take a long, long time. We can pull the curtain over this area, I think.

Comments (15) + TrackBacks (0) | Category: Diabetes and Obesity | Drug Development | The Central Nervous System | Toxicology


COMMENTS

1. Tommy Chong on October 2, 2008 12:14 PM writes...

I am not a pharmacologist, but who thought that antagonizing a receptor - which when filled by window-box grown agonist makes the patient happy and mellow - would not make one unhappy and unmellow?

Permalink to Comment

2. Timothy Leary on October 2, 2008 1:27 PM writes...

"I am not a pharmacologist, but who thought that antagonizing a receptor - which when filled by window-box grown agonist makes the patient happy and mellow - would not make one unhappy and unmellow?"

And I would further posit that blockade of the 5-HT2A receptor will cause you to act like Dick Cheney.

Permalink to Comment

3. satan on October 2, 2008 3:44 PM writes...

The worst ideas always begin with 'experts' saying-

" We are different"
" This time is different"
" This cannot happen to us"
" This is a new paradigm"

Ironically, 'experts' are always caught flat-footed when the paradigm changes or things are different.

Permalink to Comment

4. ex-UK Pharma on October 3, 2008 2:46 AM writes...

Ah, the antagonist / inverse agonist cannabionoid game. My former employers had a CB1 project, I was peripherally involved doing some in-vitro functional screening.

It seemed as though every project meeting was a reverse on the previous one. "We want an antagonist". Next meeting "Actually, maybe an inverse agonist would be better, let's chase that". Lather, rinse, repeat.

Permalink to Comment

5. Petros on October 3, 2008 8:09 AM writes...

Don't forget that one of the efefcts of smoking weed is "the munchies"

So CB1 receptor activation appears to stimulate appetite.

Permalink to Comment

6. Petros on October 3, 2008 8:18 AM writes...

Quite a few in development

otenabant Pfizer Phase III antagonist

drinabant sanofi-aventis phase II antagonist
surinabant sanofi-aventis phase II antagonist
ibipinabant Solvay/BMS phase II antagonist
AZD-2207 AstraZeneca phase II antagonist

Org-50189 Schering Plough phase I antagonist
AZD-1175 AstraZeneca phase I antagonist
rosonabant Esteve Phase I inverse agonist

Permalink to Comment

7. Selene on October 3, 2008 2:19 PM writes...

So Pfizer's candidate now has a name? They list it in their Sept 30 pipeline update as a number and AFAIK always have done so.

Also considering the lack of success of rimonabant and now taranabant, how much time and effort is sanofi likely to put into those phase II candidates?

Permalink to Comment

8. Maks on October 4, 2008 1:38 PM writes...

Does anyone know why almost all CB1 antagonists are actually inverse antagonists? Is is just "bad" chemistry or an intrinsic property? The only one I'm familiar with which is a silent agonist is cannabivarin which is in clinical trials by GW Pharmaceuticals.

Permalink to Comment

9. leigh on October 4, 2008 10:55 PM writes...

the field doesn't know how to separate the psych effects from the energy balance effects. the cb1 receptor is so freaking ubiquitous that an antagonist/inverse agonist affects all kinds of things. i find myself asking whether they can be separated at all with our current level of skill and knowledge.

Maks, there are several compounds that appear to be neutral antagonists, but i haven't seen much research on them. the ones we hear about, and the ones generally used in study of cb1 receptors, happen to have inverse agonist properties. rimonabant is a long-lived staple in cb pharmacology.

Permalink to Comment

10. rosie on October 5, 2008 1:10 PM writes...

I am sorry, but I believe in this drug! I have been taking it slightly less than 2 years and have terrific results with no bad side effects! I will be very sorry to go to the clinic tomorrow to turn in un-used pills and end the study. I just hope another one (as good) comes along!

Permalink to Comment

11. Dr. Helen Bin on October 18, 2008 8:19 AM writes...

"I am sorry, but I believe in this drug! I have been taking it slightly less than 2 years and have terrific results with no bad side effects! I will be very sorry to go to the clinic tomorrow to turn in un-used pills and end the study. I just hope another one (as good) comes along..."

I completely agree, but would like to state the opinion and special expert addition ...

Permalink to Comment

12. Petros on October 27, 2008 8:31 AM writes...

And now the EU has pulled Accomplia on safety grounds.

Permalink to Comment

13. Petros on November 6, 2008 6:53 AM writes...

And now Pfizer has pulled otenabant (in phase III) saying it showed no adverse effects but citing the unfavourable regulatory climate!

Permalink to Comment

14. Kat on February 2, 2009 7:27 PM writes...

Hi - I took Acomplia from September 2006 through the pull last November. All I can say is that after 40 years trying to battle my weight to no avail, Acomplia helped me drop 50lb and did not alter my mood adversely. I do realize that the incidence of depression is high 8% - but I believe with appropriate monitoring, this drug is a Godsend for those that tolerate it.

Permalink to Comment

15. Kat on February 2, 2009 7:28 PM writes...

Hi - I took Acomplia from September 2006 through the pull last November. All I can say is that after 40 years trying to battle my weight to no avail, Acomplia helped me drop 50lb and did not alter my mood adversely. I do realize that the incidence of depression is high 8% - but I believe with appropriate monitoring, this drug is a Godsend for those that tolerate it.

Permalink to Comment

POST A COMMENT




Remember Me?



EMAIL THIS ENTRY TO A FRIEND

Email this entry to:

Your email address:

Message (optional):




RELATED ENTRIES
The Palbociclib Saga: Or Why We Need a Lot of Drug Companies
Why Not Bromine?
Fragonomics, Eh?
Amicus Fights Its Way Through in Fabry's
Did Pfizer Cut Back Some of Its Best Compounds?
Don't Optimize Your Plasma Protein Binding
Fluorinated Fingerprinting
One of Those Days