could this be what the infamous neuro gang is referring to when they say freezing, falling and gait dysfunction are nondopaminergic? the second pathway, the indirect pathway? see below from Addex website:
commmunication solves many problems. i hope these aren't all gene therapy deliveries. vague announcements are my pet peeve,
Addex is working with Merck, who from what i am seeing so far is creating it's own brand name sinemet shortage through 2011. Global redistribution of sinemet it says, literally, in a letter to doctors. get used to the idea that you may have to switch to generic sometime in the not too distant future. let's hope they make enough of my kind, another generic doesn't work for me. I won't mention names but Lord knows why.
these molecules are the latest - they were very abundant at BIO with just letter and number identification. sounds promising and i'm glad about the possibilities, but trust no one unfortunately.
From the addex website:
mGluR4 activation (mGluR4 PAM)
Published research shows that mGluR4 activators, like those in development in a
collaboration between Addex and Merck & Co., Inc., could work via two distinct mechanisms to alleviate symptoms of Parkinson’s disease and, potentially, even slow the progression of the disease:
1) mGluR4 activation triggers a compensatory mechanism, mediated by glutamate, that may spare and/or potentiate the use of dopamine receptor activators;
2) mGluR4 activation may have neuroprotective effects that help preserve the brain’s dopaminergic neurons, thus delaying progression of the disease.
Dopamine functions in the brain at the top of the basal ganglia motor circuit, which is composed of two pathways —
the “direct” pathway and the “indirect” pathway — that regulate signaling to the thalamus via two brain regions in the basal ganglia system: the substantia nigra pars reticulate (SNr), and the internal globus pallidus (GPi).
Both direct and indirect pathways target the thalamus via a non-dopaminergic mechanism (GABA signaling).
The direct and indirect pathways
balance each other. The direct pathway exerts an inhibitory effect on SNr/GPi signaling, while the indirect pathway exerts an excitatory effect; both must operate in balance for the thalamus to allow normal motor function.
The belief is that this rebalanced signaling will restore proper motor circuit function. Since mGluR4 modulators do not result in dopaminergic stimulation, patients could be spared the neurological side effects associated with dopamine-related therapies, such as the dyskinesia (involuntary movements) caused by levodopa.
http://www.addexpharma.com/key-indic...nsons-disease/
paula