How Prozac gets its groove on.
A very cool anouncement this morning: Researchers at New York's Cold Spring Harbor laboratory say that they have identified the manner in which the antidepressant drug Prozac has its effect. We've known for many years now that drugs like Prozac have an antidepressant effect, but the fine level details of how the drugs work have not been known.
Prozac is part of a class of drugs known as SSRIs, or Selective Serotonin Reuptake Inhibitors. These drugs are believed to produce their effect by altering the ease with which Serotonin, a neurotransmitter chemical naturally found in the brain, gets reabsorbed from the synapses (spaces) between brain cells. An electrical impulse runs down the length of an entire brain cell whenever that cell (called a neuron) is activated. When the electrical impulse reaches the end of the cell, it triggers the release of neurotransmitter chemicals like serotonin. These neurotransmitter chemicals flood into the space between the neurons and stimulate the next cells in line to activate with their own electrical impulses. Once these next cells in line have "fired", the job of the neurotransmitter chemicals is done, and they need to get out of the synapse so that they won't overstimulate their targets. This is typically accomplished by having the original cell that released the neurotransmitters suck them back up.
In depression, so the theory goes, there is a problem with the normal chemical transmission of neural impulses. As I recall it, the post-synaptic cells (those in line to be activated) are not sensitive enough to respond to normal amounts of transmitter chemical, and/or, not enough chemical is released into the synapse. The net result is that too few neural impulses end up successfully bridging the synaptic gaps. Prozac and drugs like it are thought to have their effect by making sure that Serotonin stays in the gap for an extra long time, thus amplifying the effect of the pre-synaptic impulses, and making it so that more post-synaptic neurons are stimulated.
If the story ended there it would be interesting enough, but it doesn't end there. SSRIs like Prozac and other anti-depressants do not work like other drugs you are familiar with. Their antidepressant effect is not sudden, and not terribly related to how much of the drug is in the blood or brain at any given moment. Rather, it takes some time for the drugs to have their effect; several weeks in general. Thus, the effect of Prozac is not direct but rather, indirect. It is not just that Prozac keeps more serotonin in the synapses that causes the antidepressant effect. Rather, the presence of Prozac and similar drugs actually triggers the synapse itself to grow and change over time so that it becomes more sensitive to the amount of Serotonin appearing in the synapse, even as more serotonin remains in the synapse. It does this by growing new "Serotonin receptors" on the post-synaptic neuron cell membranes, and even by growing new neurons, I am to believe. With more new "baskets" available with which to collect Serotonin, more signal gets passed over to the post-synaptic neuron telling it when to fire. That synapses are altered over time by the presence of Prozac and similar SSRIs is not news, but exactly what chain of events transpires to make it happen has been a mystery.
Todays annoucement is part of the unravelling of this particular mystery:
"By profiling the telltale marker proteins produced by different kinds of cells in the brains of adult mice, the researchers first defined discrete steps in the complex process, called neurogenesis, that converts unspecialized stem cells into mature, specialized neurons."
"Next, knowing that Prozac treatment somehow increases the number of neurons in the brain, the researchers tested which step in the neurogenesis pathway might be stimulated by Prozac. They found that Prozac treatment specifically stimulates the generation of a kind of cells they dubbed "amplifying neural progenitors" or ANPs--the second step in the neurogenesis pathway from stem cells to mature neurons."
Facinating stuff, and entirely new. This sort of unraveling of the brain's mechanisms is exactly the sort of finding that will help the drug companies to create better, more targeted antidepressants in the near future, for they will now know with greater clarity what levers within the brain they need to push on to achieve an efficient antidepressant effect.
The press release from the Cold Spring Harbor Laboratory is available here; the HealthDay news article based on the press release is here, and the full report will be available in the May 23rd, issue of Proceedings of the National Academy of Sciences.
Prozac - Allan N. Schwartz, PhD - Jul 4th 2009
While I cannot cite any studies off hand and I wish prozac did help improve memory for dementia patients, to the best of my knowledge, it does not have any impact on dementia (alzheimers).
effects of Prozac on cognitive ability? - Norman Serra - Jul 4th 2009
Does anyone know if there have been tests on Alzheimer's patients to determine the effects of Prozac on cognitive ability?