Ergotamine derivatives

A series of corresponding ergoline and ergolene derivatives was synthesized. The ergotamine derivative showed an interesting antihypertensive activity. Unfortunately, the substance has very poor solubility and stability and therefore the further pharmacological evaluation was stopped (ref. 25). 

Methysergide is an ergotamine derivative that impacts central serotonin balance.51 It is reserved for use in migraineurs refractory to other agents, due to its significant adverse-effect profile. As an ergot compound, it is a vasoconstrictor that may worsen vascular dilatory reserves and precipitate cardiovascular events or ischemic stroke in those with... 

Ergotamine derivatives Monitor cardiovascular complications as for serotonergic agents. 

Uses Postpartum bleeding (uterine subinvolution) Action Ergotamine derivative Dose 0.2 mg IM after placental deliv y, may repeat 2-4-h intervals or 0.2-0.4 mg PO q6-12h for 2-7 d Caution [C, ] Contra HTN, PRO Disp Inj, tabs SE HTN, N/V Interactions t Vasoconstriction W/ ergot alkaloids, sympathomimetics, tobacco EMS Tobacco use can t vasoconstriction and lead to a hypertensive crisis OD May cause N/V/D, chest/abd pain, limb numbness, and possibly distal gangrene d/t vasoconstriction activated charcoal may be effective for PO form... 

Mecfianism of Action An ergotamine derivative, alpha-adrenergic blocker that directly stimulates vascular smooth muscle. May also have antagonist effects on sero-fonin. Therapeutic Effect Peripheral and cerebral vasoconstriction. Pharmacokinetics Slow, incomplete absorption from the gastrointestinal (GI) tract rate of absorption of intranasal route varies. Protein binding greaterthan 90%. Undergoes extensive first-pass metabolism in liver. Metabolized to active metabolite. Eliminated in feces via biliary system. Half-life 7-9 hr. 

Mechanism of Action An ergotamine derivative and alpha-adrenergicblocker that directly stimulates vascular smooth muscle, resulting in peripheral and cerebral vasoconstriction. May also have antagonist effects on serotonin. Therapeutic Effect Suppresses vascular headaches. 

Ergotamine is an ergot derivative indicated for the treatment of migraine. Amitriptyline and propranolol can be used for the prophylaxis of migraine. 

Ergot alkaloids were the first adrenoblockers to be studied. Despite the fact that the majority of ergot alkaloids exhibit a-adrenoblocking activity, their pharmacology is often different. In terms of chemistry, ergotamine and ergonovine are derivatives of lysergic acid. 

Dihydroergotamine, a hydrogenated derivative of ergotamine, differs mainly in its degree of activity. It has less vasoconstrictive action than ergotamine, is 12 times less active as an emetic and has less oxytocic effect. 

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