Spectral Map of Neuroleptics

Spectral map of 45 neuroleptic (antipsychotic) compounds in 12 pharmacological tests in rats. Red circles denote compounds and green squares represent tests. The most polarizing tests are apomorphine, epinephrine and tryptamine. (Spectramap is a trademark of Coloritto BV.)

The figure shows a biplot in which the horizontal and vertical axes represent the two most important factors as computed by Spectral Map Analysis (SMA) of the log double-centered activities of 45 neuroleptic (antipsychotic)compounds determined in 12 pharmacological tests. The two factors explain 73 and 12 percent of the variance in the log double-centered data, respectively.

On the biplot, red circles represent compounds and green squares respresent tests. The sizes of the circles are proportional to the potency (average activity of tests) of the compounds. The sizes of the squares are proportional to the sensitivity (average activity of compounds) of the tests.

Circles that appear close together on the biplot are associated with compounds whose profiles (after correction for their differences in potency) are similar. Likewise, squares that are lying close together possess profiles (after correction for differences in sensitivity) that are similar. Note that circles and squares may lie close together while having different sizes.

The center of the biplot is indicated by a cross, and indicates the compound and test with average profile. Circles and squares that are positioned at a distance from the center are associated with compounds and tests whose profiles deviate from the average.
Three groups of tests appear to polarize the spectral map of the neuroleptics, namely:   Apomorphine and Amphetamine on the right lower side, Norepinephrine and Epinephrine on the left lower side and Tryptamine and Ptosis (closure of eyelids) above the center. These are the three poles of the map by which all other features of the map can be explained. They correspond with activities of the neuroleptics on three distinct receptors for neurotransmitters in the brain, namely receptors for dopamine, norepinephrine and serotonin, respectively.

The spectral map allows the construction of bipolar axes between any pair of tests. For example, the horizontal calibrated axis is drawn through the representations of Apomorphine and Norepinephrine. These are the two poles of the bipolar axis Apomorphine/Norepinephrine. This axis represents the contrast between effects of neuroleptic compounds on the dopamine and norepinephrine receptors in the brain. (Note that the axis is calibrated logarithmically.)
Vertical projection of the compounds (circles) upon the bipolar axis of the two tests provides an approximate reading of the corresponding ratios of activities. For example, the apomorphine to norepinephrine ratio of ED50s for Haloperidol is about 30, and the corresponding ratio for Chlorpromazine is about 0.1. This indicates that Haloperidol is about 300 times more specific for the dopamine receptor than for the norepinephrine receptor when compared to Chlorpromazine. This bipolar axis represents the known dopamine/norepinephrine contrast between neuroleptic compounds. Similar bipolar axes have been drawn through the representations of Tryptamine and Apomorphine, and through Tryptamine and Norepinephrine. These two bipolar axes represent additional contrasts between neuroleptic compounds.

This spectral map represents a meaningful two-dimensional classification of these 45 neuroleptics, based on their effects on three receptors for neurotransmitters, namely dopamine (Apomorphine test), norpinephrine (Norepinephrine test) and serotonin (Tryptamine test). This map reproduces 85 percent of the the ratios between the 12 pharmacological tests.

Looking at the map one perceives that the areas on the right and left lower sides (close to the Apomorphine and Norepinephrine poles) are densily populated with compounds. The area above the center (close to the Tryptamine pole), however, is occupied by only three compounds, each with very low potency. Most of the 45 neuroleptics represented on the map have affinities (in varying proportions) for the dopamine and norepinephrine receptors, but only three of them possess an additional affinity for the serotonin receptor. In 1975 this charted a “terra incognita” on the map, which was waiting to be explored. About twenty years later, neuroleptic compounds with high potency and high affinity for both the dopamine and serotonin receptors came to the market. These are the so-called "atypical neuroleptics" of which a claim is made that they not only control the previously mentioned positive symptoms of (so-called) schizophrenia (such as hallucinations) but also the negative ones (such as social withdrawal).

This application shows that the type of Multivariate Data Analysis described here is not only capable of producing meaningful classifications of known entities, but also allows theprediction of yet undiscovered ones. This is characteristic for the Scientific Method, which has led to great insight and progress.
It is often the case that only a few (hidden) factors account for the multiplicity of phenomena that we observe. This is Thurstone’s approach to human intelligence and Plato’s view of the world, which we have discussed above.

The figure was produced by the program Spectramap designed by the author (P. J. Lewi) and Jul Van Hoof from data published by Paul A. J. Janssen et al. (1965). (Spectramap is a trade name owned by Coloritto BV.)

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Date created: December 20, 2005         Date last modified: September 6, 2006