Why is Native Dopamine Not Used?
Endogenous dopamine plays a critical physiological role in endocrine regulation. At the level of the anterior pituitary, it acts as a natural inhibitory factor: it suppresses the secretion of prolactin (lactotroph hormone) and decreases the release of growth hormone (GH).
Given this, one might expect native dopamine to be the logical treatment for hormone excess. However, the native neurotransmitter has strict pharmacological limitations and cannot be used to correct endocrine disorders. There are two main reasons for this: it has an extremely short duration of action and is completely unable to cross the blood-brain barrier (BBB). To overcome this, pharmacology utilizes dopamine receptor agonists—medications that mimic the effects of the natural neurotransmitter while lacking its pharmacokinetic drawbacks.
Bromocriptine: The Classic Approach
Bromocriptinum is a classic representative of this group, acting as a semisynthetic ergot alkaloid derivative. Its pharmacodynamics rely on direct stimulation of postsynaptic dopamine receptors in the central nervous system.
The drug effectively reduces pathological secretion of prolactin and GH, and also possesses significant antiparkinsonian activity.
Indications for use:
- Acromegaly (indicated when surgical resection is not feasible for various reasons).
- Hyperprolactinemic states accompanied by galactorrhea and prolactin-dependent amenorrhea.
- Medical suppression of physiological lactation when clinically indicated.
Strict contraindications include severe forms of arterial hypertension, occlusive vascular diseases, and Huntington's chorea.
Side Effects of Bromocriptine
Because bromocriptine acts non-selectively, its use is frequently accompanied by adverse effects. Their pathogenesis is directly linked to the distribution of stimulated receptors across various organ systems:
- Chemoreceptor trigger zone of the vomiting center: Activation of this area predictably causes nausea and vomiting.
- Cerebral cortex: Excess stimulation can provoke psychotic reactions, including delusions and hallucinations.
- Extrapyramidal system: Interference with dopaminergic pathways here leads to motor disturbances, such as dyskinesias.
- Peripheral circulation: The drug can cause orthostatic hypotension and peripheral arterial vasospasm. Clinically, this vasospasm often manifests as painful calf muscle cramps.
Other less specific adverse reactions include dry mouth and constipation.
Cabergoline: A Modern Alternative
Cabergolinum is a modern agent that largely surpasses bromocriptine in clinical utility.
Its key distinguishing feature is high selectivity—cabergoline is a selective $D_2$ receptor agonist. The second major advantage is a significantly longer duration of action. After administration, the hypoprolactinemic effect persists for 7 to 28 days, making therapy much more convenient for the patient.
It is important to consider the dose-dependent effects of cabergoline:
- At therapeutic doses, the drug acts precisely, suppressing the secretion exclusively of pituitary lactotroph cells.
- At high doses, selectivity decreases, leading to systemic effects of central $D_2$ receptor stimulation.
Indications for cabergoline are entirely analogous to those for bromocriptine.