Medical Pharmacology Chapter 23:  Ergot Alkaloids

• Organ Systems

  • CNS:

    •   Hallucinogenic-- LSD:

      • Peripheral (5-HT₂) serotonin receptor peripheral antagonist

      • Behavioral effects: agonist presynaptic or postsynaptic 5 HT₂ effects.

    •   Dopamine Receptor Interactions:

      • Extrapyramidal system

      • Prolactin release regulation:

        • Bromocriptine (Parlodel) and pergolide (Permax) specificity for pituitary dopamine receptors

          1. Suppression of pituitary prolactin secretion: by activating regulatory dopamine receptors

          2. Bromocriptine (Parlodel) and pergolide (Permax) are competitive with dopamine and other dopamine agonists (apomorphine) at binding sites

  • Vascular Smooth Muscle:

    •  Ergotamine (unrelated compounds) are mainly vasoconstricting.

      • Vasoconstriction: partially blocked by α-adrenergic receptor blocking drugs--

        • Suggesting vasoconstriction by ergot alkaloids may be due to partial agonist effects at α adrenergic receptors

      • Vasoconstriction is long-lasting.

        • α-adrenergic receptor effects

        • 5-HT receptor-mediated effects

      • Vasoconstriction is associated with differential vascular sensitivity to ergot alkaloids

        • Most sensitive: cerebral arteriovenous anastomotic vessels to these agents:

          1.  Ergotamine

          2.  Dihydroergotamine 

          3.  Sumatriptan (Imitrex) 

        • Antimigraine specificity is mediated by neuronal or vascular serotonin receptors

      • Most-common drugs used for migraine treatment:

        • Ergotamine

        • Ergonovine

        • Methysergide (Sansert)

      •   Overdosage (ergotamine and related agents)

        • Severe, long-lasting vasospasm

          • Not reversible by α-antagonists

          • Not reversible by serotonin antagonists

  • Uterine Smooth Muscle

    • Stimulant action: involves serotonergic, alpha-adrenergic, and other effects

    • Uterine sensitivity changes during pregnancy (possibly due to progressively increasing numbers of alpha₁ receptors

    • Small doses: rhythmic uterine contraction and relaxation

    • Larger doses: substantial, prolonged contractions

    • Ergonovine: more uterine selective (agent of choice for obstetric uses)

  • Other Smooth Muscle:

    • Bronchiolar smooth muscle: no effect

    • Gastrointestinal smooth muscle: variable sensitivity {nausea, diarrhea, and vomiting -- occurs with variability in required dosage probation impatient}

      •  Mechanism of Action:

        1. Activation of gastrointestinal serotonin receptors

        2. CNS emetic centers

Burkhalter, A, Julius, D.J. and Katzung, B. Histamine, Serotonin and the Ergot Alkaloids (Section IV. Drugs with Important Actions on Smooth Muscle), in Basic and Clinical Pharmacology, (Katzung, B. G., ed) Appleton-Lange, 1998, pp 261-286.;  New "Triptans" and Other Drugs for Migraine, The Medical Letter, Vol. 40 (Issue 1037); October 9, 1998