1. Histamine and 5-HT

// Histamine

02.07.21 | 15:08 tags:


  • Autocoids are molecules that are autocrine

denoting or relating to a cell-produced substance that has an effect on the cell by which it is secreted.



  • Histamine has 4 receptors
H1Allergy Inflammation & Stimulates RAS (promotes wakefulness)
H3Pre-synaptic cleftBRAKEH3 inverse agonist - Used for narcolepsy - e.g: Tiprolisant/Pitlisan

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H1 Blockers

  • First generation Anti-histamincs
    • Crosses Blood-brain barrier
    • Can cause sedation - Thus contraindicated in
    • Anticholenergic properties - thus for indications such as
      • Motion sickness
      • Drug-induced parkinsonism
      • Muscular Dystonias
    • However side-effects

Adverse Effects - Sedation, drowsiness, lack of concentration, headache, fatigue - Psychomotor incoordination - GIE - nausea, vomiting, loss of appetite (anorexia), epigastric discomfort - Anticholinergic sideffects such as: cause dryness of mouth, blurring of vision, constipation, urinary retention.


  • Allergic conditions
  • Insect bite, ivy poisoning, and to prevent histamine release
  • P - Possess - Parkinsonism
  • A - Anti - Acute Muscular Dystonia
  • C - Cholinergic - Common Cold
  • P - Properties - Prophylaxis of motion sickness
  • Second generation

    • Cannot cross blood brain barrier - thus no sedation
    • No Anti-cholinergic activity
    • Useful only for allergy
    • Cetirizine - an active metabolite of hydroxyzine (1st gen H1 Blocker) is one of the commonly used second-generation antihistamines. In addition to H1 -blocking effect, it can also inhibit the release of histamine. It causes minimal/or no drowsiness. It is not metabolized in the body. Incidence of cardiac arrhythmias is rare with this drug.
      • Levo-cetrizine, a L-isomer is more potent and less sedative
  • Third generation:

    • Some authorities describe the term 3rd generation antihistaminics for the active enantiomer (like levo-cetirizine) or metabolite (e.g. desloratidine and fexofenadine) of 2nd generation drugs.

Cisapride Astemizole Terfenadine These drugs are withdrawn due to cause of Torsades de pointes Metabolized by 3A4 enzyme, thus inducers led to toxicity



ReceptorLocationActionDrugAnt/agonistUsesSide effects
1B/1DBlood vessels of brainVasoconstriction-triptanAgonistMigraine
5HT2A/2cClozapine, OlanzapineBlockerAtypical AntipsychoticsWeight gain/Lipodystrophy syndrome
FLibAnSERINAntagonistHSSD - Hypoactive Sexual Desire Disorder
5HT3Chemoreceptor trigger zoneEmesis/vomiting-SetronsBlockersDOC for chemotherapy/radiotherapy/Post-op induced vomiting
5HT4GITPeristalisisMosapride, CisaprideAgonist/ProkineticsGERDs [However DOC- PPI]


  • Unilateral pulsatile headache
  • Inflammation and dilatation of blood vessels of the brain
  • Calcitonin-gene related peptide (CGRP) is released from the trigeminal nerve
    • Causes inflammation
    • Powerful vasodilator
  • DOC is NSAIDs
  • -triptans (serotonin (5-HT1) receptor agonists, sumatriptan derivatives) are DOC for severe acute attacks


  • Triptans stimulatates this receptor

  • It causes vasoconstriction in the blood vessel

  • It inhibits the release of CGRP from trigeminal nerve

  • Ergotamine also stimulates 5Ht1B/D

    • However increased vomitting is associated thus they aren’t preferred
  • Ergotamine and triptans should not be given together

  • Coronary artery spasm is a possible sideeffect due to vasoconstriction
  • Thus avoided in patients with Coronary Artery Disease


Antiepileptic DrugsValproate
BBeta blockersProponolol - DOC for prophylaxis of migraine
Botulinum toxin (Onabotulinum toxin A)Used especially when all other drugs fail
CCalcium Channel BlockersFlunarizine
CGRP MABsErenumab, Framanezumab, Galcanezumab
MigraineMethysergide - risk of pulmonary fibrosis
MABsEren-umab, Framanezumab, Galcanezumab
  • Calcitonin-gene related peptide (CGRP) is released from the trigeminal nerve - which has 5HT1B/1D and 5HT1F
    • 5-HT1F stimulation leads to decreased CGRP and prevents from vasodilation and
    • e.g: Lasmiditan - part of ditans
    • Calcitonin gene-related peptide receptor antagonists -GEPAnt
      • Olcegepant