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    Brainware University: (BP501T) Class Notes (Medicinal Chemistry-II Theory)

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    Mriganka Karmakar
    Histamine is a biogenic amine that is synthesized locally from the amino acid histidine. It is stored in mast cells and basophils and released during allergic reactions. Upon release, it acts on four types of G protein-coupled histamine receptors (H1-H4) to produce various physiological effects. Histamine is synthesized via histidine decarboxylase and degraded through methylation or oxidative deamination pathways. It plays important roles in gastric acid secretion, allergic responses, and neurotransmission.

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    Brainware University: (BP501T) Class Notes (Medicinal Chemistry-II Theory)

    Uploaded by

    Mriganka Karmakar
    197 views6 pages
    Histamine is a biogenic amine that is synthesized locally from the amino acid histidine. It is stored in mast cells and basophils and released during allergic reactions. Upon release, it acts on four types of G protein-coupled histamine receptors (H1-H4) to produce various physiological effects. Histamine is synthesized via histidine decarboxylase and degraded through methylation or oxidative deamination pathways. It plays important roles in gastric acid secretion, allergic responses, and neurotransmission.

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    Unit I Histamine

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    Histamine is a biogenic amine that is synthesized locally from the amino acid histidine. It is stored in mast cells and basophils and released during allergic reactions. Upon release, it acts on four types of G protein-coupled histamine receptors (H1-H4) to produce various physiological effects. Histamine is synthesized via histidine decarboxylase and degraded through methylation or oxidative deamination pathways. It plays important roles in gastric acid secretion, allergic responses, and neurotransmission.

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    197 views6 pages

    Brainware University: (BP501T) Class Notes (Medicinal Chemistry-II Theory)

    Uploaded by

    Mriganka Karmakar
    Histamine is a biogenic amine that is synthesized locally from the amino acid histidine. It is stored in mast cells and basophils and released during allergic reactions. Upon release, it acts on four types of G protein-coupled histamine receptors (H1-H4) to produce various physiological effects. Histamine is synthesized via histidine decarboxylase and degraded through methylation or oxidative deamination pathways. It plays important roles in gastric acid secretion, allergic responses, and neurotransmission.

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    BRAINWARE UNIVERSITY

    [BP501T] CLASS NOTES [Medicinal Chemistry-II Theory]

    HISTAMINE

    Introduction

    Histamine, meaning ‘tissue amine’ (histos—tissue) is almost ubiquitously present in animal tissues and
    in certain plants, e.g. stinging nettle. It was implicated as a mediator of hypersensitivity phenomena
    and tissue injury reactions. It is now known to play important physiological roles. Histamine is present
    mostly within storage granules of mast cells. Tissues rich in histamine are skin, gastric and intestinal
    mucosa, lungs, liver and placenta. Nonmast cell histamine occurs in brain, epidermis, gastric mucosa
    and growing regions. Turnover of mast cell histamine is slow, while that of nonmast cell histamine is
    fast. Histamine is also present in blood, most body secretions, venoms and pathological fluids.

    Chemistry of Histamine

    Histamine, known trivially as 4(5-)(2-aminoethyl)imidazole, structurally is composed of an imidazole


    heterocycle and ethylamine side chain. The methylene groups of the aminoethyl side chain are
    designated α and β. The side chain is attached, via the β-CH2 group, to the 4-position of an imidazole
    ring. The imidazole N at position 3 is designated the pros (π) N, whereas the N at position 1 is termed
    the tele (Ʈ) N. The side chain N is distinguished as Nα.

    Synthesis of histamine

    Histamine is β imidazolylethylamine. It is synthesized locally from the amino acid histidine and
    degraded rapidly by oxidation and methylation.

    Histamine is synthesized in Golgi apparatus of its principal storage cells, mast cells, and basophils.
    Histamine is formed from the naturally occurring amino acid L-hisitidne (S-histidine) via the catalysis
    of either the pyridoxal phosphate dependent enzyme histidine decarboxylase (HDC, EC 4.1.1.22) or L-
    aromatic amino acid decarboxylase (L-AAAD). Substrate specificity is higher for HDC versus L-AAAD.
    HDC inhibitors (HDCIs) include α-fluoromethylhistidine (FMH), a mechanism-based inhibitor, and
    certain flavonoids.7 Although useful as pharmologic probes, HDCIs have not proved to be useful
    clinically.

    Histamine metabolism

    There are two major paths of histamine metabolism in humans. The more important is ring
    methylation to form N-methylhistamine, catalyzed by histamine-N-methyltransferase, which is
    distributed widely. Most of the N-methylhistamine formed is then converted to N-methylimidazole
    acetic acid by monoamine oxidase (MAO), and this reaction can be blocked by MAO inhibitors.
    Alternatively, histamine may undergo oxidative deamination catalyzed mainly by the nonspecific
    enzyme diamine oxidase, yielding imidazole acetic acid, which is then converted to imidazole acetic
    acid riboside. These metabolites have little or no activity and are excreted in the urine. Measurement
    of N-methylhistamine in urine affords a more reliable index of histamine production than assessment
    of histamine itself. Artifactually elevated levels of histamine in urine arise from genitourinary tract
    bacteria that can decarboxylate histidine. In addition, the metabolism of histamine appears to be
    altered in patients with mastocytosis such that determination of histamine metabolites is a more
    sensitive diagnostic indicator of the disease than histamine.

    1
    BRAINWARE UNIVERSITY
    [BP501T] CLASS NOTES [Medicinal Chemistry-II Theory]

    Histamine metabolism

    Storage and Release

    Histamine is found in almost all mammalian tissues in concentrations ranging from 1 to more than 100
    µg/g. Mast cells and histamine are in particularly high concentration in skin and the mucosal cells of
    the bronchi, intestine, urinary tract, and tissues adjacent to the circulation. It is found in higher
    concentrations in mammalian cerebrospinal fluid than in plasma and other body fluids.

    In mast cells, histamine (positively charged) is held by an acidic protein and heparin (negatively
    charged) within intracellular granules. When the granules are extruded by exocytosis, Na+ ions in e.c.f.
    exchange with histamine to release it free.

    2
    BRAINWARE UNIVERSITY
    [BP501T] CLASS NOTES [Medicinal Chemistry-II Theory]

    Mechanism of antigen-antibody reaction induced release of histamine from mast cell.

    In sensitized atopic individual, specific reaginic (IgE) antibody is produced and gets bound to Fc epsilon
    receptor I (FcεRI) on the surface of mast cells. On challenge, the antigen bridges IgE molecules
    resulting in transmembrane activation of a tyrosine-protein kinase (t-Pr-K) which phosphorylates and
    activates phospholipaseCγ. Phosphatidyl inositol bisphosphate (PIP2) is hydrolysed and inositol
    trisphosphate (IP3) is generated which triggers intracellular release of Ca2+. The Ca2+ ions induce
    fusion of granule membrane with plasma membrane of the mast cell resulting in exocytotic release of
    granule contents. In the granule, positively charged histamine (Hist+) is held complexed with
    negatively charged protein (Prot–) and heparin (Hep–) molecules. Cationic exchange with extracellular
    Na+ (and Ca2+) sets histamine free to act on the target cells.

    3
    BRAINWARE UNIVERSITY
    [BP501T] CLASS NOTES [Medicinal Chemistry-II Theory]

    Histamine Receptors

    4
    BRAINWARE UNIVERSITY
    [Course Code] CLASS NOTES [Course Name]

    Histamine induced gastric acid secretion

    Histamine induced gastric acid secretion

    2022-23 Prepared by: Faculty Name (Department of Pharmaceutical Technology


    Brainware University, Barasat)
    BRAINWARE UNIVERSITY
    [Course Code] CLASS NOTES [Course Name]

    Pharmacological Actions of Histamine

    Pathophysiological role of Histamine

    2022-23 Prepared by: Faculty Name (Department of Pharmaceutical Technology


    Brainware University, Barasat)

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