dopetalk does not endorse any advertised product nor does it accept any liability for it's use or misuse

This website has run out of funding so feel free to contribute if you can afford it (see footer)

Author Topic: Novel drugs for depression (discusses Ketamine)  (Read 401 times)

Offline Chip (OP)

  • Server Admin
  • Hero Member
  • *****
  • Administrator
  • *****
  • Join Date: Dec 2014
  • Location: Australia
  • Posts: 6464
  • Reputation Power: 0
  • Chip has hidden their reputation power
  • Gender: Male
  • Last Login:Yesterday at 10:50:37 AM
  • Deeply Confused Learner
  • Profession: IT Engineer
Novel drugs for depression (discusses Ketamine)
« on: October 17, 2016, 02:53:51 PM »
source: http://www.economist.com/news/science-and-technology/21708655-new-generation-drugs-could-change-way-depression-treated-novel-drugs

Sniffing at a new solution

Novel drugs for depression

A new generation of drugs could change the way depression is treated



IT STARTED out as LY110141. Its inventor, Eli Lilly, was not sure what to do with it. Eventually the company found that it seemed to make depressed people happier. So, with much publicity and clever branding, Prozac was born. Prozac would transform the treatment of depression and become the most widely prescribed antidepressant in history. Some users described it as “bottled sunshine”. It attained peak annual sales (in 1998) of $3 billion and at the last count had been used by 54m people in 90 countries. And, along the way, it embedded into the public consciousness a particular idea about how depression works—that it is caused by a chemical imbalance in the brain, which the drug corrects. Unfortunately, this idea seems to be only part of the story.

In science it is good to have a hypothesis to frame one’s thinking. The term “chemical imbalance” is just such a thing. It is a layman’s simplification of the monoamine hypothesis, which has been the prevalent explanation for depression for almost 50 years. Monoamines are a class of chemical that often act as messenger molecules (known technically as neurotransmitters) between nerve cells in the brain. Many antidepressive drugs boost the level of one or other of these chemicals. In the case of Prozac, the monoamine in question is serotonin.

The monoamine hypothesis, though, is under attack. One long-standing objection is that, although drugs such as Prozac raise levels of their target monoamine quite quickly, the symptoms of depression may take weeks, or even months to abate—if, indeed, they do abate, for many patients do not respond to such drugs at all. Now, to add to that, a second objection has emerged. This is the discovery that ketamine, a drug long used as an anaesthetic and which is also popular recreationally, works, too, as a fast-acting antidepressant. Ketamine’s mode of action is not primarily on monoamines, so the race is on to use what knowledge there is of the way it does work to design a new class of antidepressant. This is a change of direction so radical that some think it heralds a revolution in psychiatry.

Special K

Ketamine works for 75% of patients who have been resistant to other forms of treatment, such as Prozac (which works in 58% of patients). Moreover, it works in hours, sometimes even minutes, and its effects last for several weeks. A single dose can reduce thoughts of suicide. As a result, although it has not formally been approved for use in depression, it is widely prescribed “off label”, and clinics have sprouted up all over America, in particular, to offer infusions of the drug (which must be taken intravenously, if it is to work). Anecdotal reports suggest that it has already saved many lives.

Ketamine’s rise has been gradual. The discovery of its efficacy against depression happened a decade ago. Conducting clinical trials of new uses for drugs whose patents have expired is not a high priority for pharmaceutical companies, which generally prefer to test new molecules whose patents they own—and without such trials, formal approval for a new use cannot be forthcoming. Now, though, novel ketamine-related treatments are emerging.

One such is esketamine. Normal ketamine is a mixture of two molecules that are mirror images of each other. Esketamine is just one of these “optical isomers”. Though it, too, is off-patent, Johnson & Johnson, a large American drug company that is developing it for use, hopes it will have the same positive effects as the unsorted isomeric mixture, but without side-effects such as hallucinations, dizziness and “dissociation”—a feeling of being awake but detached from one’s surroundings.

By changing its formulation so that it can be administered in the form of a nasal spray, the firm both makes esketamine easier to use than isomerically mixed ketamine and creates something patentable. Preliminary evidence suggests esketamine does indeed work, and the firm is seeking approval for it to be used to treat two conditions: major depressive disorder with imminent risk of suicide, and treatment-resistant depression.

Other companies, though, are taking a different approach, by studying ketamine’s mode of action and attempting to imitate the way it works. Many people think ketamine affects the action of a common neurotransmitter called glutamate, by blocking the activity of receptors for this molecule. One hypothesis is that it interacts with a glutamate receptor called NMDA that had never previously been thought to be involved in depression. Several firms are therefore seeking to mimic the effect of ketamine by aiming at the NMDA receptor.

One such is Allergan, an Irish company that last year paid $560m to buy Naurex, an American biotech firm whose NMDA-blocking drug rapastinel is intended as a once-a-week intravenous treatment. Evidence from an early trial shows rapastinel is well tolerated, does not induce hallucinations and seems to work quickly. Allergan plans to start more extensive trials later this year. Nor is Allergan alone in its interest in the NMDA route. Other firms working on molecules that interact with this receptor, or with a special flavour of it called NR2B, include AstraZeneca, Avanir Pharmaceuticals and Cerecor.

Reception committee

It would be a mistake, though, to think that science has now reached a neat conclusion about how depression acts in the brain. One surprise came earlier this year in the form of work published by Carlos Zarate of America’s National Institutes of Health, who is a pioneer in the field. This study suggests that, in mice at least, ketamine is not working directly on the NMDA receptor, but rather on another glutamate receptor. This finding will not matter to Johnson & Johnson, because esketamine mimics the effects of normal ketamine, which is known to work. But it may mean those taking the NMDA route with other molecules are barking up the wrong tree.

As to the specifics of Dr Zarate’s study, Husseini Manji, the head of neuroscience at Johnson & Johnson, says it is possible that this work identified an additional way to generate antidepressive effects. Even if ketamine is found to work via another receptor, this does not preclude it working via NMDA. Armin Szegedi, who runs clinical development of the drug rapastinel at Allergan, makes the same argument. He explains that all the glutamate receptors seem to interact with each other as well, and act as a complicated system.

Time will tell who is correct, but such minutiae will matter less than whether one of these new approaches works. Lots of drugs, for many indications, work well, even though no one knows precisely how. The important point, though, is that ketamine has opened up a new line of attack on a horrible illness—and that this attack is being pressed relentlessly home.

This article appeared in the Print Edition with the headline: Sniffing at a new solution
« Last Edit: October 19, 2016, 11:54:04 AM by chipper »
I do not condone or support any illegal activities. All information is for theoretical discussion and wonder.
All activities discussed are considered fictional and hypothetical. Information of all discussion has been derived from online research and in the spirit of personal Freedom.

Tags:
 

Related Topics

  Subject / Started by Replies Last post
6 Replies
4564 Views
Last post December 08, 2015, 12:41:29 PM
by Snout
12 Replies
5942 Views
Last post November 11, 2015, 09:34:31 PM
by Elevated
0 Replies
474 Views
Last post January 18, 2016, 11:50:33 AM
by Z
2 Replies
843 Views
Last post January 22, 2016, 04:12:43 PM
by Zoops
13 Replies
6785 Views
Last post February 26, 2016, 07:39:51 PM
by Anti-hero
21 Replies
10238 Views
Last post July 31, 2017, 06:52:05 AM
by Tainted
6 Replies
3870 Views
Last post December 16, 2016, 04:54:31 PM
by komoshan
17 Replies
7135 Views
Last post December 08, 2018, 02:13:28 AM
by MoeMentim
4 Replies
502 Views
Last post August 18, 2017, 07:22:56 PM
by Chip
0 Replies
1786 Views
Last post April 30, 2018, 10:59:15 PM
by Chip


dopetalk does not endorse any advertised product nor does it accept any liability for it's use or misuse





TERMS AND CONDITIONS

In no event will d&u or any person involved in creating, producing, or distributing site information be liable for any direct, indirect, incidental, punitive, special or consequential damages arising out of the use of or inability to use d&u. You agree to indemnify and hold harmless d&u, its domain founders, sponsors, maintainers, server administrators, volunteers and contributors from and against all liability, claims, damages, costs and expenses, including legal fees, that arise directly or indirectly from the use of any part of the d&u site.


TO USE THIS WEBSITE YOU MUST AGREE TO THE TERMS AND CONDITIONS ABOVE


Founded December 2014
SimplePortal 2.3.6 © 2008-2014, SimplePortal