Origin and differences from natural alkaloids
The initial raw material for obtaining drugs in this group is the sclerotia of wild ergot, a parasitic fungus Claviceps purpurea that infects rye crops. Structurally, all representatives of the group are derivatives of 6-methylergoline (D-lysergic acid). The main drugs include dihydroergotamine, dihydroergototoxin, and dihydroergocryptine.
During the chemical modification (hydrogenation) process, the pharmacological profile of the molecules changes significantly. This eliminates a number of side effects characteristic of natural compounds.
| Pharmacological effect | Natural alkaloids | Dihydrogenated derivatives |
|---|---|---|
| Effect on the uterus | Increases myometrial tone | No stimulating effect |
| Direct vascular action | Pronounced vasoconstriction | Lesser vasoconstricting effect |
| $\alpha$-adrenoblocking action | Moderate | Significantly higher |
Dihydroergotamine: key drug profile
Dihydroergotamine is considered the reference standard of the group. Its mechanism of action consists of two components: non-selective blockade of $\alpha_1$- and $\alpha_2$-adrenoceptors and agonism at serotonin receptors. This determines the drug's multidirectional effect on various vascular beds.
- Peripheral effects: the drug causes pronounced dilation of peripheral vessels, which naturally leads to a decrease in systemic blood pressure (BP).
- Central effects: due to the stimulation of serotonin receptors, dihydroergotamine exerts a tonic effect on cerebral vessels.
In clinical practice, dihydroergotamine (trade name Digidergot, available as methanesulfonate/mesylate) is actively used to abort acute migraine attacks. Specific indications also include vasospastic angina and orthostatic hypotension (in the latter case, the effect is achieved through the venotonic action). The drug can be administered intranasally as a spray, parenterally, or taken orally as drops.
Combination drugs and analogues
In addition to pure alkaloids, combinations and synthetic analogues with an expanded spectrum of action are widely used in medicine.
Vasobral (Vasobral) A combination drug containing the dihydrogenated alkaloid dihydroergocryptine and the trimethylxanthine caffeine. The pharmacodynamics of the agent boil down to $\alpha$-adrenoceptor blockade followed by vasodilation. Vasobral is prescribed for cerebrovascular diseases, the recovery period after stroke, peripheral circulation disorders, and cochleovestibular disorders (hearing and balance impairments).
Nicergoline (Nicergoline) This drug is an analogue of ergot alkaloids. Its structure features an ergoline ring connected to a bromine-substituted nicotinic acid residue, which provides a dual mechanism of action:
- $\alpha$-adrenoblocking activity.
- Myotropic spasmolytic activity.
Nicergoline causes pronounced dilation of cerebral and peripheral vessels while having only a mild effect on systemic blood pressure. In addition, the drug inhibits platelet aggregation and possesses a nootropic effect (improves memory and attention). It is used for chronic cerebrovascular insufficiency, migraine, and peripheral blood flow disorders. It is important to note that the drug is taken before meals, and its therapeutic effect develops slowly, requiring a prolonged course lasting many months.
Proroxan (Pyrroxan)
Proroxan stands out among other agents for its ability to block both peripheral and central $\alpha_1$- and $\alpha_2$-adrenoceptors. Its effect on receptors within hypothalamic structures is of particular clinical significance.
Adrenoceptor blockade in the periphery, predominantly in arterioles and precapillaries, leads to vasodilation and a decrease in blood pressure. In addition to its hypotensive effect, proroxan exerts sedative, anti-withdrawal, and antipruritic effects.
The drug is in demand for stopping hypertensive and sympathoadrenal crises (especially in hypothalamic syndrome with high blood pressure). It is also successfully used in narcology to relieve morphine or alcohol withdrawal syndrome, in dermatology for pruritic allergic dermatoses, as well as for vestibular disorders, including Ménière's disease and motion sickness.
Briefly: answers to topical questions
What are the symptoms of ergot poisoning (ergotism)?
Symptoms of ergot poisoning (ergotism) depend on the form of the disease.
- Acute form — symptoms of acute gastroenteritis and CNS involvement: paresthesia, convulsions.
- Chronic form — sensation of "crawling ants", especially in the extremities, vomiting, gastrointestinal disorders; infertility is possible.
Clinical forms of ergotism:
- Convulsive — toxic tonic convulsions, predominantly of flexor muscles.
- Gangrenous — necrosis of the peripheral parts of the extremities, accompanied by severe pain.
- Mixed form.
Remembering the differences between dihydrogenated and natural alkaloids is aided by the rule of "three M's": Fewer vascular spasms, More powerful $\alpha$-blockade, Uterus at rest (no effect on the myometrium).
Class and exam questions
Why is dihydroergotamine effective for migraines if it dilates peripheral vessels?
In the periphery, the drug indeed acts as an $\alpha$-adrenoblockers, causing vasodilation. However, within the CNS, it acts as a serotonin receptor agonist, which leads to the toning and constriction of excessively dilated cerebral vessels, aborting a migraine attack.
What are the advantages of nicergoline over other drugs in the group?
Nicergoline combines $\alpha$-adrenoblocking action and myotropic spasmolytic activity due to its nicotinic acid residue. It significantly improves cerebral circulation, exhibits a nootropic effect, while having a minimal impact on systemic blood pressure.
In which crises is the prescription of proroxan indicated?
Proroxan is effective in hypertensive and sympathoadrenal crises, especially if they occur against the background of hypothalamic syndrome, as the drug blocks adrenoceptors directly within hypothalamic structures.
What else to study on this topic
- Pathophysiology of migraine and the role of cerebral serotonin receptors.
- Features of orthostatic hypotension and the venotonic mechanism of dihydroergotamine.
- The effect of nicergoline on blood rheological properties and platelet aggregation.
- The role of the hypothalamus in the development of sympathoadrenal crises.
- Mechanisms of withdrawal syndrome development in alcoholism and drug addiction.
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