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D(2) dopamine receptor Adenylate cyclase type 2 Amine oxidase [flavin- containing] B Synaptic vesicular amine transporter Sodium- dependent dopamine transporter Sodium- dependent dopamine transporter Tyrosine 3-monooxygenase Aromatic-L- amino-acid decarboxylase Catechol O- methyltransferase Dopamine Safinamide cAMP Safinamide Safinamide Dopamine Dopamine Dopamine Safinamide L-Tyrosine Tetrahydrobiopterin O2 L-Dopa Dihydrobiopterin H2O CO2 S-Adenosylmethionine 3-Methoxytyramine S-Adenosylhomocysteine H2O O2 Homovanillin H2O2 NH3 ATP PPi Magnesium FAD Fe2+ Pyridoxal 5'-phosphate Neuronal Excitability Magnesium Post synaptic neuron Synapse Cytosol Presynaptic Neuron Cytosol Postsynaptic Neuron Diffusion Blood-Brain Barrier Safinamide is transported in the neurons by thedopamine reuptake transporter. Since Parkinson's disease is caused by low level of dopamine in the substantia nigra, the effect of the drug brings the level of dopamine to a normal and higher level. Dopamine activates the D2 (dopamine) receptors. This causes the phosphorylation of many proteins and the decrease of the concentration in cAMP. Low levels of cAMP decreases neuronal excitability in the striatum. Synaptic Vesicle Striatum Since the two types of dopamine receptors are on different neurons, the action of dopamine in high levels results in the fine control of motor symptoms. Safinamide inhibits amine oxidase B (MAO B) catalyzing the metabolism of dopamine. This results in higer levels of dopamine in the neurons cytosol.
DRD2 ADCY2 MAOB SLC18A2 SLC6A3 SLC6A3 TH DDC COMT Dopamine Safinamide cAMP Safinamide Safinamide Dopamine Dopamine Dopamine Safinamide L-Tyrosine Tetrahydrobiopterin Oxygen L-Dopa Dihydrobiopterin Water Carbon dioxide S- Adenosylmethionine 3- Methoxytyramine S- Adenosylhomocysteine Water Oxygen Homovanillin Hydrogen peroxide Ammonia Adenosine triphosphate Pyrophosphate Neuronal Excitability