New target.
drug molecules interact with the rat version of a receptor of the human glutamate.
Richard Harper, Jon Erickson and Daniel Robertson / Eli Lilly and Co.
scientists are excited about what they see as a possible breakthrough in the treatment schizophrenia: the first human trials showing the effectiveness of a new class of antipsychotic drugs. The study represents the "leading edge of a new generation of drugs" for schizophrenia, says Yale University researcher John Krystal drug.
During the last half century, many drugs were developed to treat schizophrenia, which affects about 1% of the population but each of them have activity on the same target.. the dopamine D2 receptor the "dopamine hypothesis" is based on the fact that the excess of dopamine causes psychosis.
in recent years, however, scientists have been probing another theory, the "glutamate hypothesis." Glutamate is the major excitatory neurotransmitter in the brain and activates other neurochemicals. The theory is that the low activity in some type of glutamate receptor (NMDA) paradoxically leads to excess glutamate also damage the brain connections. This results in psychosis, thought disorder, and numbing of emotions associated with schizophrenia. In animal studies, compounds that act on glutamate receptors appear to block the effects of amphetamines better than do most conventional drugs mimicking psychosis.
In an article published online Sunday Nature Medicine , researchers from Eli Lilly and Co. in Indianapolis, Indiana, have shown that these compounds work in humans too.
The team, led by Sandeep Patil and Darryle Schoepp, compared a compound called LY140023 both placebo and conventional antipsychotic olanzapine. The randomized trial included 118 patients with schizophrenia who spent four weeks closely monitored in hospital. More than a third of patients in both treatment groups responded with 25% or more reduction in symptoms using a standard scale - compared to only 3% in the placebo group. The difference between treatment groups was not statistically significant; However, those taking LY140023 did not show parkinsonian movement problems or weight gain, two side effects of conventional antipsychotic drugs.
"I could not exaggerate this exciting breakthrough," says Jeffrey Conn of Vanderbilt University in Nashville, Tennessee, who worked on medication for schizophrenia for Merck & Co. "It is the first clear demonstration that you can get an antipsychotic efficacy without inhibiting the D2 dopamine receptors. "Conn said the new drug may be targeting brain pathways" downstream "of those applied by conventional antipsychotic drugs. Thus, it is said it, the medicament "may be closer to the primary pathology" of schizophrenia.
Related Sites
- More information on schizophrenia
- More information about glutamate receptors and the hypothesis of glutamate
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