Dopamine receptor agonists

Mechanism of action and receptor profile

The main principle of action of this group of medicinal products is direct stimulation of dopamine receptors located in the structures of the neostriatum.

The drugs have a specific receptor profile. As a rule, they exhibit the highest pharmacological activity toward D2 receptors.

Classification includes non-selective agonists that affect both D1 and D2 receptors simultaneously. This category includes pergolide, bromocriptine, and pramipexole. Furthermore, pramipexole has an important feature: in addition to D2, it also stimulates D3 receptors.

By their chemical nature, some representatives (pergolide and bromocriptine) are ergot alkaloid derivatives.

Pharmacodynamics using bromocriptine as an example

Bromocriptine (Bromocriptine) is a classic representative of the group of direct dopamine receptor agonists (predominantly of the D2 type). By origin, it is a semisynthetic derivative of the ergot alkaloid ergocryptine.

Its action in the body is characterized by two key directions:

• Antiparkinsonian effect: achieved through active stimulation of D2 receptors localized in the neostriatum.
• Endocrine effect: the drug is capable of stimulating pituitary D2 receptors. This action naturally leads to a marked decrease in prolactin release from the anterior pituitary.

Clinical application and dosing regimens

Dopamine receptor agonists possess a critically important pharmacokinetic advantage: they exceed levodopa in duration of action. This determines their place in treatment regimens.

• Bromocriptine and pergolide are primarily prescribed as part of combination therapy together with levodopa. This combination is especially relevant when the clinical efficacy of levodopa is insufficient or if the patient develops the specific "on-off" motor syndrome.
• Pramipexole is considered a more effective agent than bromocriptine. Due to this, it is successfully used both in combination with levodopa and as monotherapy.

Side effects and ways to manage them

Therapy with direct agonists may be accompanied by a number of adverse reactions, which are conventionally divided into early-onset and long-term effects.

Early-onset effects:

1. Orthostatic hypotension.
2. Dyspeptic disorders (nausea and vomiting). The mechanism of nausea is associated with stimulation of D2 receptors in the trigger zone of the vomiting center. To correct this condition, domperidone, a peripheral dopamine receptor blocker that does not cross the blood-brain barrier, is prescribed.

Specific reactions to pramipexole:

• Drowsiness.
• Sudden sleep attacks.

Long-term effects:

• Mental disorders, including the development of hallucinations and psychoses.
• Movement disorders in the form of dyskinesias.

Differences from other antiparkinsonian agents

Within the classification of antiparkinsonian drugs, it is necessary to clearly distinguish direct agonists from agents of other groups:

• Levodopa is a metabolic precursor of dopamine, not a direct agonist.
• Carbidopa is an inhibitor of the enzyme DOPA decarboxylase, used strictly in combination with levodopa.
• Selegiline acts as an MAO-B inhibitor, preventing the enzymatic inactivation of dopamine.
• Trihexyphenidyl (cyclodol) belongs to the group of central M-anticholinergics.

Class and exam questions

What else to study on this topic

• Mechanisms of development of the "on-off" syndrome during long-term therapy
• Pharmacodynamics of domperidone and anatomy of the vomiting center trigger zone
• Comparative characteristics of semisynthetic ergot alkaloid derivatives
• The role of D3 receptors in mediating the therapeutic effects of pramipexole
• Pathogenesis of extrapyramidal dyskinesias and psychiatric disorders

Other topics in the section "Agents Used in Psychiatry and Neurology"

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