ErgotErgot

Ann BakerAnn BakerKatie DitterKatie Ditter

Carrie Carrie PetersonPeterson

Botanical Botanical CharacteristCharacterist

icsics• ParasiteParasite

• SclerotiumSclerotium

• ConidiaConidia

• ReproductionReproduction

History of History of ErgotErgot

• DiscoveryDiscovery• FamilyFamily• • NamesNames• • Medicinal PurposesMedicinal Purposes• FolkloreFolklore

History of LSDHistory of LSD

• • DiscoveryDiscovery

• Original PurposeOriginal Purpose

• Social ImpactSocial Impact

Chemistry of Chemistry of AlkaloidsAlkaloids• • Nitrogenous and BasicNitrogenous and Basic

• • Physiologically ActivePhysiologically Active

• • Salt and Free Amine FormationSalt and Free Amine Formation

• • SolubilitySolubility

• • Crystalline SolidCrystalline Solid

• Bitter TasteBitter Taste

The Ergot The Ergot AlkaloidsAlkaloids

• • Structure based on indole ringStructure based on indole ring• • General biosynthesis of alkaloidsGeneral biosynthesis of alkaloids• • Starting amino acid is tryptophanStarting amino acid is tryptophan

• • All ergot alkaloids are derivatives of (+)-All ergot alkaloids are derivatives of (+)-Lysergic AcidLysergic Acid

The Ergot The Ergot AlkaloidsAlkaloids

• • Structure based on indole ringStructure based on indole ring• • Starting amino acid is tryptophanStarting amino acid is tryptophan• • All ergot alkaloids are derivatives of All ergot alkaloids are derivatives of (+)-Lysergic Acid(+)-Lysergic Acid

General General Biosynthesis of Biosynthesis of

AlkaloidsAlkaloids

Biosynthesis Biosynthesis of Lysergic of Lysergic

AcidAcid

Important DerivativesImportant Derivatives

Natural Products:Natural Products:ErgonovineErgonovineErgotamineErgotamine

Semisynthetic Semisynthetic Products:Products:

Methylergonovine maleateMethylergonovine maleateDihydroergotamine mesylateDihydroergotamine mesylateLysergic acid diethylamineLysergic acid diethylamine

Synthetic Products:Synthetic Products:sumatriptan (Imitrexsumatriptan (Imitrex®)®)

1630…fed to 1630…fed to animals (all died)animals (all died)1778…duck and 1778…duck and drake fed ergotdrake fed ergot1831…fed rooster ergot extracts1831…fed rooster ergot extracts

1909…tyramine 1909…tyramine 1910…histamine1910…histamine

1884…calmodulin 1884…calmodulin alkaloidalkaloid

1906-1918…1906-1918…ergotoxine ergotoxine

and and ergotamineergotamine

History of Clinical History of Clinical TrialsTrials

Peripheral Effects

• smooth muscle contractionssmooth muscle contractions• Cures migraine headachesCures migraine headaches• lowers blood pressurelowers blood pressure

• extracts usedextracts used•Ergotamine tartrate + caffeineErgotamine tartrate + caffeine•dihydroergotaminedihydroergotamine

Uterotonic Effects

•childbirthchildbirth

•accelerate childbirthaccelerate childbirth•arrest hemorrhagingarrest hemorrhaging

•Extracts usedExtracts used•ergonovine maleateergonovine maleate•ergometrineergometrine•ergotamine (prolonged effects)ergotamine (prolonged effects)

Neurohormonal Effects

Serotonin antagonism•ExtractExtract

•methysergidemethysergide

•TreatmentsTreatments•prophylaxis for migraineprophylaxis for migraine•carciniod syndromecarciniod syndrome•rhuematic affectionsrhuematic affections

Neurohormonal Effects

Adrenergic blockade•TreatmentsTreatments•high blood pressurehigh blood pressure•cerebral circulatory disorderscerebral circulatory disorders•vascular disordersvascular disorders•cervical syndromecervical syndrome

•Extracts usedExtracts used•dihydroergocorninedihydroergocornine•dihydroergokryptinedihydroergokryptine•dihydroergocristinedihydroergocristine

Central EffectsBulbomedullary effects

•EffectsEffects•bradycardiabradycardia•vomitingvomiting•inhibition of vasomotor centerinhibition of vasomotor center•inhibition of pressoreceptor reflexesinhibition of pressoreceptor reflexes

•ExtractsExtracts•ergot alkaloids aloneergot alkaloids alone•(has sedative effect)(has sedative effect)

Central EffectsMesodrencephalic effects•EffectsEffects

•hyperthermiahyperthermia•hyperglycemiahyperglycemia•mydriasismydriasis•piloerectionpiloerection•tachypneatachypnea•hyperreflexiahyperreflexia•general motorgeneral motor•hyperactivityhyperactivity •ExtractExtract

•lysergidelysergide

LSD

ReferencesReferencesRobbers, J.E., Speedie, M.K. & Tyler, V.E. (1996) Robbers, J.E., Speedie, M.K. & Tyler, V.E. (1996) Pharmacognosy and Pharmacognosy and

Pharmacobiotechnology.Pharmacobiotechnology. Williams & Williams: Media, PA.Williams & Williams: Media, PA.

Etc.Etc.