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"It's like a magic drug", said the lead researcher of a team from Yale University in the US whose latest study suggests that ketamine, a drug normally used as an anasthetic, could be reformulated as an anti-depressant that takes effect in hours rather than the usual weeks and months of most available medications.
You can read how the researchers discovered this effect in a study they
performed on rats which was published online on 20 August in the
journal Science. Senior author Dr Ronald Duman, professor of psychiatry and pharmacology
at Yale, told the media that just one dose of the drug can work rapidly
and lasts for seven to ten days.
This is the same ketamine that is used as a recreational drug, called "Special K", or "K". He and his team found that the drug not only improved the rats'
depression-like behaviors, it also restored connections between neurons
or brain cells that had been damaged by chronic stress. They called
this "synaptogenesis".
They hope their findings will help to speed up the development of a
safe and easy to administer version of ketamine, which has already
proved to be effective in severely depressed patients, they said. About ten years ago, scientists at Connecticut Mental Health Center
found that in lower doses, ketamine, normally used as a general
anasthetic for children, appeared to relieve patients with depression. Since then, other studies have shown that over two thirds of patients
who don't respond to all other types of anti-depressants improved hours
after receiving ketamine, said Duman.
The problem with using ketamine more widely to treat depression has
been the fact it has to be given intravenously under medical
supervision, and it can also cause short-term psychotic symptoms. So Duman and colleagues decided to investigate the effect of ketamine
on the brain to see if it might reveal suitable targets for other safer
and easier to adminster drugs.
" ... the mechanisms underlying this action of ketamine [a glutamate
N-methyl-D-aspartic acid (NMDA) receptor antagonist] have not been
identified," they wrote.
They found that ketamine acts on a pathway that controls the formation
of new synaptic links between neurons, encouraging synaptogenesis; they
wrote that they observed:
" ... increased synaptic signaling proteins and increased number and
function of new spine synapses in the prefrontal cortex of rats."
Moreover, they found that a critical point on the pathway, involving
the enzyme mTOR, controls production of proteins needed to form the new
synapses.
The researchers concluded that:
"Our results demonstrate that these effects of ketamine are opposite to
the synaptic deficits that result from exposure to stress and could
contribute to the fast antidepressant actions of ketamine." Duman and colleagues told the press that they can already see ways to
sustain the rapid effect of ketamin by intervening at other points
downstream of this critical one. These could be additional targets for
new drugs. This discovery not only brings new hope to the 40 per cent or so of
patients with depression who don't respond to medication, but to many
others who only experience relief after months and sometimes years of
treatment. The researchers also noted that ketamine has already shown to be
effective as a rapid way to treat people with suicidal thoughts, many
such patients usually only respond weeks later with traditional drugs.
The National Institute of Mental Health, the Connecticut Mental Health
Center and Yale University School of Medicine paid for the study.
Zdroj:
"mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists."
Nanxin Li, Boyoung Lee, Rong-Jian Liu, Mounira Banasr, Jason M. Dwyer,
Masaaki Iwata, Xiao-Yuan Li, George Aghajanian, Ronald S. Duman
Science, 20 August 2010: Vol. 329. no. 5994, pp. 959 - 964
DOI: 10.1126/science.1190287