Pharmacology of Ergot Alkaloids

Dr. Bashir Ibrahim

8/5/2016
Ergot alkaloids are produced by Claviceps
purpurea, a fungus that infects grasses
and grains(rye) under damp conditions.
This fungus synthesizes histamine,Ach,
tyramine, in addition to 20 ergot alkaloids
These alkaloids affect -adrenoceptors,dopamine
receptors, 5-HT receptors, and other receptors.
Epidemics of ergotims due to ingestion of contaminated
grain was known since antiquity
Signs and symptoms of poisoning include dementia with
florid hallucinations,prolonged vasospasms leading to
gangrene, stimulation of uterus which may cause
abortion in pregnants.
Chemistry & pharmacokinetics:
Tow types of alkaloids:(1) amine alkaloids
include 6-
methylergoline,ergonovine(ergometrine),
lysergic acid and lysergic acid
diethylamide(LSD)
(2)peptide alkaloids include: ergotamine,
bromocriptine and -ergocryptine
Ergot alkaloids are variably absorbed from GIT. Absorption of
ergotamine may be improved by coadministration with
caffeine
Bromocriptine and cabergoline are well absorbed from GIT
Ergot alkaloids are extensively metabolized in the body.
Pharmacodynamics:
(A)Mechanism of action:
Ergot alkaloids exert their effects by
acting on different receptors. Their
effects include:
- Agonist, partial agonist ,and
antagonist effects on -adrenoceptors,5-
HT1A ,5-HT1D 5-HT2, & 5-HT3 receptors
- Agonist or partial agonist effect at central
dopamine receptors
- A powerful stimulant effect on uterus through 5-
HT2 receptors
 Organ system effects:
CNS: hallucinogenic effect.LSD is a synthetic

ergot compound with this effect by action on 5-

HT2 agonist effect in the CNS .It is a drug of
abuse.
Bromocriptine, cabergoline and pergoline act
on central dopamine receptors in the
extrapyramidal motor control nerves.They
also suppress prolactin secretion from pituitary
cells by activating regulatory dopamine
receptors.
Vascular smooth muscle : this is a drug,

species,and vessel-dependent action.

-In humans ergotamine conistricts most
vessels,an action blocked by -adrenoceptor blockers
 However ,ergotamine's effect on blood
vessels is associated with epinephrine
reversal and with blockade of the
response of other -agonists. This reflects a
partial agonist effect of the drug.
Ergotamine,ergonovine and methysergide all
have partial agonist effect on 5-HT2 vascular
receptors.This action reflects their antimigraine
effect.
Uterine smooth muscle:
-The stimulant action of ergot alkaloids
on uterus appears to combine -agonist,
serotonin and other effects.
-sensitivity of uterus to ergot alkaloids increases during
pregnancy, may be due to increased -adrenoceptors.
In very small doses ergot alkaloids exert rhythmic
contractions of uterus.In large doses they produce
powerful prolonged cotraction.Ergonovine is the most
selective.
Other smooth muscle Organs:
GIT is quite sensetive, nausea,vomiting and diarrhea may
be induced even with small doses.
 i
Clinical uses of ergot alkaloids:
Migraine headache: ergotamine
tartarate is effective when given during
the prodrome of an attack. It is available
as oral, sublingual, rectal suppositories
and inhalar use. It is often combined with
caffeine to facilitate absorption
Dihydroergotamine 0.5-1mg injection is
used for intractable migraine
Methysergide was used for prophylaxis
but is withdrawn due to toxicity.
 Hyperprolactinemia: this causes amenorrhea,
infertility in women and galactorrhea in both
sexes
-bromocriptine reduces the high levels of
prolactin that results from pituitary tumors.
Cabergoline is similar but more potent
Postpartum hemorrhage: ergonovine maleate

is given to control postpartum hemorrhage

after delivery.Oxytocin is the preferred agent.
 Diagnosis of varient angina: IV ergonovine
produceces prompt vasoconistriction
during coronary angiography to diagnose
varient angina

Senile cerebral Insufficiancy:

dihydroergotoxine is used for the relief of
senility and treatment of Alzheimer's
dementia.Rationale is not clear.
 Toxicity & contraindications:
-GIT disturbances including
diarrhea,nausea and vomiting
-prolonged vasospasm in over dose of
ergotamine and ergonovine, which
may result in gangrene
-chronic therapy with methysergide
was associated with connective tissue
proliferation in the retroperitoneal
space, the pleural cavity,and
endocardial tissue of the heart