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Like existing agents, most emerging agents in late-stage development target the serotonin and dopamine receptors.
The combination of ITI-007's high-potency blockade of 5HT2A receptors and unique dopamine receptor activity should allow a personalized approach to patient treatment for schizophrenia by making it possible for the first time, to select a clinical dose capable of saturating 5HT2A receptors while permitting the "dialing in" of an optimal amount of dopamine receptor modulation by simple dose adjustments using a single drug.
An imaging device then translated radioactive emissions into data on the number and extent of dopamine receptors in brain areas thought to regulate
The findings have "strong clinical implications," argues Aston-Jones, since they show which dopamine receptors influence withdrawal symptoms.
Uhl of Johns Hopkins University School of Medicine in Baltimore now reports that a second version of the D2 dopamine receptor gene - called B1 - appears more often among people who indulge heavily in several addictive drugs, including alcohol, cigarettes, marijuana, cocaine, heroin, tranquilizers, and amphetamines.
Patricia Janak, co-senior author on the paper, said: "We found that a dopamine receptor, known as the D2 receptor, controls the ability to stay focused on a task - the well-known benefit of Ritalin.
ITI-722 is a low-dose formulation of ITI-007, ITI's first-in-class 5-HT2A antagonist/ dopamine receptor protein phosphorylation modulator (DPPM), presently in clinical trials for the treatment of schizophrenia.
In both groups, the dopamine receptor gene turned up in about one-third of the volunteers.
As a dopamine receptor protein phosphorylation modulator (DPPM), ITI-007 has dual properties; it acts as a post-synaptic antagonist and as a pre-synaptic partial agonist.
Two chemical probes sought out the specific dopamine receptor gene.
Dopamine receptor agonists are suspected to have caused serious impulse control disorders in at least 710 cases reported to the Food and Drug Administration's adverse drug events database during a 10-year period.
Caffeine integrates with a dopamine receptor that regulates the flow of calcium into the cell.