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From the 13 January 1997 issue of Smart Drug News [v5n6]. Copyright (c) 1997. All rights reserved.

Pharmacological Variation

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).

Biological specificity:
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.

Chemical specificity:
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.

Specific antagonists:
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