English Reading Materials Chapter 27:Histamine INTRODUCTION Histamine and serotonin(5-hydroxytryptamine)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,prostaglandins and leukotrienes, and cytokines,they are sometimes called autacoids (Greek,"self-remedy")or local hormones in recognition of these properties. Because of their broad and largely undesirable 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 usefulness.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. I.HISTAMINE INTRODUCTION 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 and inflammatory reactions,although it plays only a modest role in anaphylaxis. Histamine plays an important role in gastric acid secretion and functions as a neurotransmitter and neuromodulator.Newer evidence indicates that histamine also plays a role in chemotaxis of white blood cells. BASIC PHARMACOLOGY OF HISTAMINE Chemistry Pharmacokinetics Histamine occurs in plants as well as in animal tissues and is a component of some venoms and stinging secretions.English Reading Materials Chapter 27: Histamine INTRODUCTION Histamine and serotonin (5-hydroxytryptamine) 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, prostaglandins and leukotrienes, and cytokines, they are sometimes called autacoids (Greek, "self-remedy") or local hormones in recognition of these properties. Because of their broad and largely undesirable 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 usefulness. 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. I. HISTAMINE INTRODUCTION 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 and inflammatory reactions, although it plays only a modest role in anaphylaxis. Histamine plays an important role in gastric acid secretion and functions as a neurotransmitter and neuromodulator. Newer evidence indicates that histamine also plays a role in chemotaxis of white blood cells. BASIC PHARMACOLOGY OF HISTAMINE Chemistry  Pharmacokinetics Histamine occurs in plants as well as in animal tissues and is a component of some venoms and stinging secretions