Table 1.
Mechanism of action and indications of dopamine precursors and dopaminergic agonist and antagonist drugs.
| Drug | Mechanism of Action | Indications |
|---|---|---|
| Precursors | ||
| Levodopa (L-DOPA) | Levodopa mimics the role of endogenous dopamine; crosses the blood–brain barrier through various pathways, and is decarboxylated to form dopamine stimulating the dopamine receptors | Parkinson’s disease [29,30] |
| L-phenylalanine | Precursor of tyrosine, dopamine, norepinephrine (noradrenaline) and epinephrine (adrenaline) | Antidepressant effects Vitiligo [31,32] |
| L-tyrosine | Precursor of dopamine, norepinephrine and epinephrine |
Antidepressant [31,33] |
| Receptor agonists | ||
| Apomorphine | A nonergoline dopamine agonist with binding affinity to dopamine D2, D3, and D5 receptors | Parkinson’s disease [29,42,48] |
| Bromocriptine | Ergoline derivative with strong agonist activity on the D2 dopamine receptors | Parkinsonian Syndrome Amenorrhea Galactorrhea Acromegaly Premenstrual syndrome Female infertility [29,42] |
| Cabergoline | Ergoline derivative; dopamine agonist (with a high affinity for D2 receptors) and prolactin inhibitor. | Hyperprolactinemic disorders. Parkinsonian Syndrome [29,49,50] |
| DA | Agonist to the D1, D2, D3, D4, D5 dopamine receptors. Interacts on the synaptic terminals, causing neuronal excitation or inhibition at the target neuron | Hemodynamic imbalances Blood pressure Hypotension Poor perfusion of vital organs Low cardiac output [29,51] |
| Fenoldopam | Benzazepine derivative; selective dopamine D1 receptor agonist. Decreases peripheral vascular resistance in renal capillary beds | Hypertension [29,52] |
| Lisuride | Ergoline derivative, agonist to dopamine D2 receptors. It can be an antagonist to dopamine D1 receptors. Additionally, activates some serotonin receptors | Parkinson’s disease [27,29] |
| Piribedil | Nonergoline, piperazine derivative, dopamine agonist that acts on D2 and D3 receptors | Parkinson’s disease [53] |
| Pramipexole | Nonergoline, a dopamine agonist showing specificity and strong activity at dopamine D2 receptors | Parkinson’s disease Restless legs syndrome [54,55] |
| Quinagolide | Nonergoline derivative; it selectively binds to D2 receptors on the surface of lactotroph cells, resulting in reduced adenylyl cyclase activity and inhibition of prolactin secretion from the anterior pituitary | Hyperprolactinemia [27,29] |
| Ropinirole | Nonergoline derivative, selectively binds to dopamine D2 receptors, with highest affinity at D3 receptors | Parkinson’s disease Restless legs syndrome [56,57] |
| Rotigotine | Nonergoline derivative; a nonselective agonist of dopamine receptors with higher affinity at D3 receptors | Parkinson’s disease Restless legs syndrome [29,42] |
| Experimental agonists | ||
| Dihydrexidine (LS-186,899) | Selective full agonist at the dopamine D1 receptors. It has some affinity for the D2 receptor | Scientific research [58,59] |
| Pukateine | Aporphine derivative; agonist at the D2 dopamine receptor and antagonist at the α1 adrenergic receptor | Scientific research [60,61] |
| Quinpirole | Selective D2 and D3 receptor agonist | Scientific research [62,63] |
| SKF 38393 | A selective D1-like receptor agonist | Scientific research [64] |
| Antagonists and receptor blockers | ||
| Typical antipsychotics | ||
| Chlorpromazine | Phenothiazine derivative. It binds strongly to the D2 receptor, blocking its action; this blockade, in the nigrostriatal pathway, is responsible for its extrapyramidal side effects | Schizophrenia, Bipolar disorder Acute psychosis, Nausea and vomiting Relief of apprehension before surgery Persistent singultus (chronic hiccups) [29,46,65] |
| Fluphenazine | Phenothiazine derivative. Blocks postsynaptic mesolimbic dopaminergic D2 receptors in the brain | Management of psychosis in schizophrenia [29,66] |
| Haloperidol | It is a first-generation antipsychotic and one of the most frequently used worldwide. It is not selective for the D2 receptor, but, has a strong antagonism to this dopamine receptor in mesolimbic and mesocortical pathways in the brain | Schizophrenia Tourette syndrome Behavioral disorders in children Hyperactivity [29,45] |
| Loxapine | Dibenzoazepine tricyclic derivative. Antagonist with high affinity for the D2 receptor, also a serotonin 5-HT2 blocker | Schizophrenia Other psychotic disorders [27,67] |
| Molindone | Indole derivative. Antagonizes dopamine D2 receptor sites in the reticular limbic systems in the brain, decreasing dopamine activity | Schizophrenia [27,29] |
| Perphenazine | Phenothiazine derivative. It binds to the dopamine D1 and dopamine D2 receptors inhibiting their activity. Its antiemetic effect is mainly due to blockade of D2 receptors in the chemoreceptor trigger zone and the vomiting center | Schizophrenia Other psychotic disorders Nausea and vomiting [27,29] |
| Pimozide | Diphenylbutylpiperidine derivative. It binds and inhibits the dopamine D2 receptor | Tourette syndrome Schizophrenia [27,42] |
| Thioridazine | Phenothiazine derivative. It blocks postsynaptic mesolimbic dopaminergic D1 and D2 receptors | Schizophrenia Other psychotic disorders Generalized anxiety disorder Depressive disorders [27,68] |
| Thiothixene | Thioxanthene derivative. Is a highly potent antagonist of the D1, D2, D3 and D4 dopamine receptors. | Schizophrenia [27,29] |
| Atypical antipsychotics | ||
| Amisulpride | Benzamide derivative. It is a selective dopamine D2 and D3 receptor antagonist | Schizophrenia Nausea and vomiting [27,29] |
| Clozapine | Dibenzodiazepine derivative. It binds to the D4 dopamine receptors with a higher affinity than D2 receptor. Additionally, it has antagonistic effects at 5-HT2A receptors and is a partial agonist at 5-HT1A receptors | Resistant schizophrenia [27,69] |
| Olanzapine | Thienobenzodiazepine derivative. It exerts its action primarily on dopamine D1, D2, D3 and D4 and serotonin 5-HT2A, 5-HT2C, 5-HT3 and 5-HT6 receptors, blocking their action | Schizophrenia, Bipolar disorder [27,70] |
| Quetiapine | Thiazepine derivative. Antagonizes to D2 dopamine receptors and to 5-HT2A receptors (it has strong affinity for the latter) | Schizophrenia Bipolar disorder Major depressive disorder [27,71] |
| Risperidone | Benzisoxazole derivative. It blocks D2, but more 5-HT2A receptors in the brain. | Schizophrenia, Bipolar mania Autism-associated irritability [29,72] |
| Sulpiride | Benzamide derivative. Selective antagonist at dopamine D2, D3 receptors | Schizophrenia [27,29] |
| Ziprasidone | Benzothiazolylpiperazine derivative. Binds to 5-HT2A and dopamine D2 receptors with high affinity | Schizophrenia Bipolar mania Acute agitation in schizophrenic patients [29,73] |
| Antiemetics | ||
| Domperidone | Benzimidazole derivative. It has strong affinity for the D2 and D3 dopamine receptors, blocking their activity | Peristaltic stimulant, Dyspepsia, Indigestion, Epigastric pain Nausea and vomiting [27,29,74] |
| Metoclopramide | Benzamide derivative. Inhibit dopamine D2 and serotonin 5-HT3 receptors | Nausea and vomiting Gastroesophageal reflux disease [29,75] |
| Prochlorperazine | Phenothiazine derivative. It mainly blocks the D2 dopamine receptors in the mesolimbic system | Schizophrenia, Schizoaffective Other conditions with psychosis symptoms Nausea and vomiting [29,76] |
| Experimental antagonists | ||
| Eticlopride | Antagonizes D2 dopamine receptor | Scientific research [77] |
| Raclopride | Potent and selective antagonist on D2/D3 dopamine receptors | Trials studying Parkinson’s disease [29,78] |
| SCH23390 | Highly potent and selective of D1 dopamine receptor | Scientific research of drug addiction [79] |