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A healthy 45-year-old physician attending a reunion in a vacation hotel developed dizziness, redness of the skin over the head and chest, and tachycardia while eating. A short time later, another physician at the table developed similar signs and symptoms with marked orthostatic hypotension. The menu included a green salad, sauteed fish with rice, and apple pie. What is the probable diagnosis? How would you treat these patients?

It has long been known that many tissues contain substances that, when released by various stimuli, cause physiologic effects such as reddening of the skin, pain or itching, and bronchospasm. Later, it was discovered that many of these substances are also present in nervous tissue and have multiple functions. Histamine and serotonin (5-hydroxytryptamine, 5-HT) are biologically active amines that function as neurotransmitters and are found in non-neural tissues, have complex physiologic and pathologic effects through multiple receptor subtypes, and are often released locally. Together with endogenous peptides (see Chapter 17), prostaglandins and leukotrienes (see Chapter 18), and cytokines (see Chapter 55), they constitute the autacoid group of drugs.

Because of their broad and largely undesirable peripheral effects, neither histamine nor serotonin has any clinical application in the treatment of disease. However, compounds that selectively activate certain receptor subtypes or selectively antagonize the actions of these amines are of considerable clinical value. This chapter therefore emphasizes the basic pharmacology of the agonist amines and the clinical pharmacology of the more selective agonist and antagonist drugs. The ergot alkaloids, compounds with partial agonist activity at serotonin and several other receptors, are discussed at the end of the chapter.


Histamine was synthesized in 1907 and later isolated from mammalian tissues. Early hypotheses concerning the possible physiologic roles of tissue histamine were based on similarities between the effects of intravenously administered histamine and the symptoms of anaphylactic shock and tissue injury. Marked species variation is observed, but in humans histamine is an important mediator of immediate allergic (such as urticaria) and inflammatory reactions, although it plays only a modest role in anaphylaxis. Histamine plays an important role in gastric acid secretion (see Chapter 62) and functions as a neurotransmitter and neuromodulator (see Chapters 6 and 21). Newer evidence indicates that histamine also plays a role in immune functions and chemotaxis of white blood cells.


Chemistry & Pharmacokinetics

Histamine occurs in plants as well as in animal tissues and is a component of some venoms and stinging secretions.

Histamine is formed by decarboxylation of the amino acid l-histidine, a reaction catalyzed in mammalian tissues by the enzyme histidine decarboxylase. Once formed, histamine is either stored or rapidly inactivated. Very little histamine is excreted unchanged. The major metabolic pathways involve conversion to N-methylhistamine, methylimidazoleacetic acid, and imidazoleacetic acid (IAA). Certain ...

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