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From the 13 January 1997 issue of Smart Drug News [v5n6].
Copyright (c) 1997. All rights reserved.
Despite the fundamental simplicity of the receptor-substrate
concept, there is a wide range of biological effects that can
manifest. To illustrate, we will describe the binding of two well
known and thoroughly characterized compounds that have opposite
pharmacological properties. Ethanol (alcohol) is a
non-specific substance which affects a number of tissues (which,
incidentally, is very similar in scope and action to most adaptogens).
In contrast, histamine (an endogenous amine released locally
from damaged tissues) is a very specific substance with a narrow
focus of effects (which is quite representative of most Western
pharmaceuticals both OTC and prescription).
Ethanol has biological effects at
10^-2 to 10^-1 M (molar concentration) while histamine works
at 10^-8 to 10^-5 M. This makes histamine 4-6 orders of magnitude
(1000-100,000 times) more potent on a molecule by molecule basis.
These molar concentrations of histamine are not extraordinary;
there are reports of effects of various substances at 10^-9 to
10^-12 M (e.g., serotonin on mollusc hearts).
Ethanol causes a general
inhibitory effect on most cells and tissues which is uniform
and non-specific. Histamine, in stark contrast, is very selective
and quite specific. It causes 1) contraction of bronchial smooth
muscles and relaxation of vascular smooth muscles, and 2) gastric
secretion but not salivary secretion.
Ethanol is very similar in its
pharmacology to a number of other simple organic molecules (such
as diethyl ether, chloroform, and halothane). The potency of these
simple substances are more related to lipid solubility (a
physicochemical property) than organic structure or molecular
conformation. In stark contrast, small changes in the organic
structure of histamine has a large effect on its pharmacology and
potency. Compound A (blue; transposed N in the ring) has only about
1/1000th the potency of histamine in smooth muscle. Compound B
(red; addition of a methyl group) has quasi-normal histamine activity
in some tissues and deficient histamine activity in others.
Unlike ethanol, histamine has
many antagonists which block its effects by binding to histamine
receptors in tissues, and preventing its pharmacological actions.
This also provides clear evidence for the existence of specific
receptors for the histamine-blocking drugs (antihistamines), which
are used during allergy season to block the histamine-induced
contraction of bronchiolar and GI smooth muscle [Rang and Dale,
1987; Katzung, 1989]. GL