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cAMP-dependent protein kinase type II-beta regulatory subunit D(1A) dopamine receptor Adenylate cyclase type 2 cAMP-dependent protein kinase catalytic subunit alpha cAMP-dependent protein kinase catalytic subunit beta cAMP-dependent protein kinase type I-alpha regulatory subunit cAMP-dependent protein kinase catalytic subunit gamma cAMP-dependent protein kinase type I-beta regulatory subunit cAMP-dependent protein kinase type II-alpha regulatory subunit Alpha-1A adrenergic receptor Sodium- dependent dopamine transporter Sodium- dependent noradrenaline transporter Synaptic vesicular amine transporter Synaptic vesicular amine transporter Voltage- dependent calcium channel subunit alpha-2/delta-1 Voltage- dependent calcium channel subunit alpha-2/delta-2 Voltage- dependent N-type calcium channel subunit alpha-1B Voltage- dependent calcium channel subunit alpha-2/delta-1 Voltage- dependent calcium channel subunit alpha-2/delta-2 Voltage- dependent N-type calcium channel subunit alpha-1B Dopamine beta- hydroxylase Aromatic-L- amino-acid decarboxylase Tyrosine 3-monooxygenase Tyrosine 3-monooxygenase Aromatic-L- amino-acid decarboxylase Guanine nucleotide- binding protein G(s) subunit alpha isoforms short cAMP Ca+ Norepinephrine Ca+ Dopamine Dopamine Norepinephrine Solriamfetol Solriamfetol Norepinephrine Dopamine Ca+ Ca+ Solriamfetol Solriamfetol Solriamfetol Solriamfetol Dopamine Ascorbic acid O2 Dehydroascorbic acid H2O L-Dopa CO2 L-Tyrosine L-Tyrosine L-Dopa CO2 ATP PPi GTP Pyrroloquinoline quinone Copper Pyridoxal 5'-phosphate Fe2+ Fe2+ Pyridoxal 5'-phosphate Neuronal Excitability Gq Signalling cascade Magnesium Activation of D1 dopamine receptors activates the Gs signalling cascade which leads to increased cAMP. Reward Pathway Limbic System Activation of Alpha-1A receptors activates the Gq signalling cascade which has a variety of excitatory effects on neurons in the brain. Norepinephrine activates neurons in the locus coeruleus which activates the limbic system. The lymbic system is implicated in emotions and cognition. Increased cAMP results in increased neural excitability in the Limbic System which helps regulate the cognition. Limbic System Emotions Cognition Cytosol Presynaptic Neuron The inhibition of norepinephrine reuptake receptors by Solriamfetol causes more norepinephrine to accumulate in the synapse, causing the continual activation of the alpha-1A adrenergic receptor Synapse Synaptic Vesicle The inhibition of dopamine reuptake receptors by Solriamfetol causes more dopamine to accumulate in the synapse, causing the continual activation of the D1 Dopamine receptor Presynaptic Neuron Cytosol Synaptic Vesicle Postsynaptic Neuron Cytosol Dopamine is produced in the Ventral Tegmental Area of the brain Norepinephrine is produced in the locus coeruleus Prefrontal Cortex Cytosol Synapse Increased dopamine activates D1 dopamine receptor in the limbic system Increased norepinephrine activates Alpha-1A adrenergic receptorsthe limbic system Postsynaptic Neuron Blood-Brain Barrier Diffusion Blood-Brain Barrier Diffusion
PRKAR2B DRD1 ADCY2 PRKACA PRKACB PRKAR1A PRKACG PRKAR1B PRKAR2A ADRA1A SLC6A3 SLC6A2 SLC18A2 SLC18A2 CACNA2D1 CACNA2D2 CACNA1B CACNA2D1 CACNA2D2 CACNA1B DBH DDC TH TH DDC GNAS cAMP Calcium Norepinephrine Calcium Dopamine Dopamine Norepinephrine Solriamfetol Solriamfetol Norepinephrine Dopamine Calcium Calcium Solriamfetol Solriamfetol Solriamfetol Solriamfetol Dopamine Ascorbic acid Oxygen Dehydroascorbic acid Water L-Dopa Carbon dioxide L-Tyrosine L-Tyrosine L-Dopa Carbon dioxide Adenosine triphosphate Pyrophosphate Guanosine triphosphate Neuronal Excitability Gq Signalling cascade
PRKAR2B DRD1 ADCY2 PRKACA PRKACB PRKAR1A PRKACG PRKAR1B PRKAR2A ADRA1A SLC6A3 SLC6A2 SLC18A2 SLC18A2 CACNA2D1 CACNA2D2 CACNA1B CACNA2D1 CACNA2D2 CACNA1B DBH DDC TH TH DDC GNAS cAMP Ca+ Norpp Ca+ LDP LDP Norpp Solri Solri Norpp LDP Ca+ Ca+ Solri Solri Solri Solri LDP VitC O2 DHAA H2O L-Dopa CO2 Tyr Tyr L-Dopa CO2 ATP PPi GTP Pqq Cu Pyr-5'P Fe2+ Fe2+ Pyr-5'P Neu Exc Gq Si c Mg2+ Activation of D1 dopamine receptors activates the Gs signalling cascade which leads to increased cAMP. Reward Pathway Limbic System Activation of Alpha-1A receptors activates the Gq signalling cascade which has a variety of excitatory effects on neurons in the brain. Norepinephrine activates neurons in the locus coeruleus which activates the limbic system. The lymbic system is implicated in emotions and cognition. Increased cAMP results in increased neural excitability in the Limbic System which helps regulate the cognition. Limbic System Emotions Cognition Cytosol Presynaptic Neuron The inhibition of norepinephrine reuptake receptors by Solriamfetol causes more norepinephrine to accumulate in the synapse, causing the continual activation of the alpha-1A adrenergic receptor Synapse Synaptic Vesicle The inhibition of dopamine reuptake receptors by Solriamfetol causes more dopamine to accumulate in the synapse, causing the continual activation of the D1 Dopamine receptor Presynaptic Neuron Cytosol Synaptic Vesicle Postsynaptic Neuron Cytosol Dopamine is produced in the Ventral Tegmental Area of the brain Norepinephrine is produced in the locus coeruleus Prefrontal Cortex Cytosol Synapse Increased dopamine activates D1 dopamine receptor in the limbic system Increased norepinephrine activates Alpha-1A adrenergic receptorsthe limbic system Postsynaptic Neuron Blood-Brain Barrier Diffusion Blood-Brain Barrier Diffusion
PRKAR2B DRD1 ADCY2 PRKACA PRKACB PRKAR1A PRKACG PRKAR1B PRKAR2A ADRA1A SLC6A3 SLC6A2 SLC18A2 SLC18A2 CACNA2D1 CACNA2D2 CACNA1B CACNA2D1 CACNA2D2 CACNA1B DBH DDC TH TH DDC GNAS cAMP Ca2+ Norpp Ca2+ LDP LDP Norpp Solri Solri Norpp LDP Ca2+ Ca2+ Solri Solri Solri Solri LDP VitC O2 DHAA H2O L-Dopa CO2 Tyr Tyr L-Dopa CO2 ATP Ppi GTP Neu Exc Gq Si c