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CHEMISTRY OF HISTAMINE

(FOR B.PHARM. 5TH SEM. BP501P)

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By

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RAJ K. PRASAD (GOLD MEDALIST)

M.PHARM. PHARMACEUTICAL CHEMISTRY

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  • Histamine, structurally is composed of an imidazole heterocycle and ethylamine side chain.
  • The methylene groups of the amino ethyl 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.

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CHEMISTRY OF HISTAMINE

  • Decarboxylation of histidine forms the neurotransmitter histamine. Histidine compounds present in the human body include ergothioneine, carnosine, and dietary anserine.

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  • In unionized form, histamine has one neutral and two basic nitrogen atoms.
  • Structural modifications can increase selectivity for one receptor subtype over the others. For example, 2-methylhistamine is selective for the H1 receptor while 4-methylhistamine is H2-selective.

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  • Histamine’s imidazole ring is capable of tautomerization.
  • Molecular modeling and steric–activity relationship studies of the influence of conformational isomerism suggest the importance of trans-gauche rotameric structures is believed to be preferred at H1 and H2 receptors.

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HISTAMINE RECEPTORS AND THEIR DISTRIBUTION IN THE HUMAN BODY

  • Histamine exerts its biological function by interacting with at least three distinctly specifi c receptors H1, H2, and H3.

H1 receptors

  • The H1 receptor is found in smooth muscle of gut, bronchi, uterus, and vasculature.
  • Stimulation results in relaxation and increased permeability of the vasculature and spontaneous contractions in the smooth muscle of the uterus, gut, and bronchi.

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H2 receptors

  • The H2 receptor is found in the parietal cells of the stomach and in vascular smooth muscle, hepatocytes, and various blood cells.
  • Stimulation of H2 receptors in the stomach leads to an increase in gastric acid secretion.

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H3 Receptors

  • The H3 receptor is found primarily in the central nervous system (CNS).
  • Stimulation by histamine results in a decrease in the release of other neurotransmitters.

H4 receptors

  • H4 receptors are found on eosinophils, neutrophils, dendritic cells, T cells, and mast cells.
  • Stimulation promotes production and release of inflammatory cytokines and mediators of chemotaxis.
  • H4 receptors mediate symptoms of autoimmune disorders and some allergic disorders (e.g., bronchial asthma, conjunctivitis, and rhinitis).

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Histamine receptor and their antagonist