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September 25, 2003
Mapping Receptor Space
by Tom Ray
I would like to share a metaphor, or image, that I use when thinking about the new pharmacology: receptor space.
Imagine a coordinate system based on receptors, one axis for each receptor ("receptor space"). This notion of "receptor space" is in the reference frame of the unmedicated brain. Drugs perturb the system from its pharmacological origin by altering the activity of transmitter and receptor systems, through increasing or decreasing transmission or transmitter levels, or up or down regulating receptor populations.
From a pharmacological point of view, the origin of the receptor space represents the state of an individual brain at any moment, without the application of any drug. When a drug is applied that binds to receptors, it shifts the balance of activity of the brain away from the origin, by a vector representing displacement along the axes corresponding to the receptors where the drug binds (and perhaps others due to secondary interactions).
The distance of the shift represents the affinity of the drug for the receptor, or the degree to which the drug activates the receptor. Negative axes could correspond to blocking or deactivation of the receptor. For convenience, I would like to refer to molecules with a non-zero value on only one axis as "on-axis", and molecules with a non-zero value on more than one axis as "off-axis".
These kinds of changes occur spontaneously and constantly in the unmedicated brain. Thus our pharmacological reference frame, of the unmedicated brain at the origin, is a very dynamic one.
| Category: Neuropharma
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