ATC Group: N04B Dopaminergic agents

Amantadine has been shown to be a low affinity antagonist at the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors. Overactivity of glutamatergic neurotransmission has been implicated in the generation of parkinsonian symptoms. In addition, amantadine specifically inhibits the replication of influenza A viruses at low concentrations.

Apomorphine is a direct stimulant of dopamine receptors and while possessing both D1 and D₂ receptor agonist properties does not share transport or metabolic pathways with levodopa. Its actions on parkinsonian motor disability are likely to be mediated at post-synaptic receptor sites.

Bromocriptine is an inhibitor of prolactin secretion and a stimulator of dopamine receptors. The areas of application of bromocriptine are divided into endocrinological and neurological indications.

Cabergoline is a dopaminergic ergoline derivative endowed with a potent and long-lasting PRL-lowering activity.

Entacapone belongs to a new therapeutic class, catechol-O-methyl transferase (COMT) inhibitors. It is a reversible, specific, and mainly peripherally acting COMT inhibitor designed for concomitant administration with levodopa preparations. Entacapone prolongs the clinical response to levodopa.

According to the current understanding, the symptoms of Parkinson’s disease are related to depletion of dopamine in the corpus striatum. Dopamine does not cross the blood-brain barrier. Levodopa, the precursor of dopamine, crosses the blood brain barrier and relieves the symptoms of the disease.

Opicapone is a peripheral, selective and reversible catechol-O-methyltransferase (COMT) inhibitor endowed with a high binding affinity (sub-picomolar). Opicapone is indicated as adjunctive therapy to preparations of levodopa/DOPA decarboxylase inhibitors (DDCI) in adult patients with Parkinson’s disease, leading to an increase of levodopa plasma levels thereby improving the clinical response to levodopa.

Piribedil is a dopaminergic agonist (stimulates dopamine receptors and the cerebral dopaminergic pathways).

Pramipexole is a dopamine agonist that binds with high selectivity and specificity to the D₂ subfamily of dopamine receptors of which it has a preferential affinity to D₃ receptors, and has full intrinsic activity. Pramipexole alleviates parkinsonian motor deficits by stimulation of dopamine receptors in the striatum. Animal studies have shown that pramipexole inhibits dopamine synthesis, release, and turnover.

Rasagiline was shown to be a potent, irreversible MAO-B selective inhibitor, which may cause an increase in extracellular levels of dopamine in the striatum. The elevated dopamine level and subsequent increased dopaminergic activity are likely to mediate rasagiline’s beneficial effects seen in models of dopaminergic motor dysfunction.

Ropinirole is a non-ergoline D₂/D₃ dopamine agonist which stimulates striatal dopamine receptors. Ropinirole alleviates the dopamine deficiency which characterises Parkinson’s disease by stimulating striatal dopamine receptors.

Rotigotine is a non-ergolinic dopamine agonist for the treatment of signs and symptoms of Parkinson’s disease and Restless Legs Syndrome.

Safinamide acts through both dopaminergic and non-dopaminergic mechanisms of action. Safinamide is a highly selective and reversible MAO-B inhibitor causing an increase in extracellular levels of dopamine in the striatum. Safinamide is indicated for the treatment of adult patients with idiopathic Parkinson’s disease (PD) as addon therapy to a stable dose of levodopa (L-dopa).

Selegiline is a selective MAO-B-inhibitor which prevents dopamine breakdown in the brain. It also inhibits the reuptake of dopamine at the presynaptic dopamine receptor. These effects potentiate dopaminergic function in the brain and help to even out and prolong the effect of exogenous and endogenous dopamine. Thus, selegiline potentiates and prolongs the effect of levodopa in the treatment of parkinsonism.

Tolcapone is an orally active, selective and reversible catechol-O-methyltransferase (COMT) inhibitor. Administered concomitantly with levodopa and an aromatic amino acid decarboxylase inhibitor (AADC-I), it leads to more stable plasma levels of levodopa by reducing metabolism of levodopa to 3-methoxy-4-hydroxy-L-phenylalanine (3-OMD). High levels of plasma 3-OMD have been associated with poor response to levodopa in Parkinson’s disease patients.