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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 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 Aromatic-L- amino-acid decarboxylase Guanine nucleotide- binding protein G(s) subunit alpha isoforms short cAMP Ca+ Norepinephrine Ca+ Dopamine Dopamine Norepinephrine Duloxetine Norepinephrine Dopamine Ca+ Duloxetine Duloxetine Dopamine Ascorbic acid O2 Dehydroascorbic acid H2O L-Dopa CO2 L-Tyrosine CO2 ATP PPi GTP Pyrroloquinoline quinone Copper Pyridoxal 5'-phosphate Fe2+ Neuronal Excitability Gq Signalling cascade Pyridoxal 5'-phosphate Magnesium Activation of D1 dopamine receptors activates the Gs signalling cascade which leads to increased cAMP. Reward Pathway 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 limbic system is implicated in emotions and cognition. Increased cAMP results in increased neural excitability in the Limbic System which helps regulate behaviour and emotional responses. Limbic System Emotions Cognition Cytosol Presynaptic Neuron The inhibition of norepinephrine reuptake receptors by Duloxetine causes more norepinephrine to accumulate in the synapse, causing the continual activation of the alpha-1A adrenergic receptor Synapse Synaptic Vesicle Dopamine is produced in the Ventral Tegmental Area of the brain Norepinephrine is produced in the locus coeruleus Frontal Cortex Cytosol Increased dopamine activates D1 dopamine receptor in the limbic system and prefrontal cortex Increased norepinephrine activates Alpha-1A adrenergic receptors the limbic system Neuron Axon Brain Post Synaptic neuron Limbic system Blood vessel - blood brain barrier Duloxetine is taken orally and absorbed from the gastrointestinal tract
PRKAR2B DRD1 ADCY2 PRKACA PRKACB PRKAR1A PRKACG PRKAR1B PRKAR2A ADRA1A SLC6A2 SLC18A2 SLC18A2 CACNA2D1 CACNA2D2 CACNA1B CACNA2D1 CACNA2D2 CACNA1B DBH DDC TH DDC GNAS cAMP Calcium Norepinephrine Calcium Dopamine Dopamine Norepinephrine Duloxetine Norepinephrine Dopamine Calcium Duloxetine Duloxetine Dopamine Ascorbic acid Oxygen Dehydroascorbic acid Water L-Dopa Carbon dioxide L-Tyrosine Carbon dioxide Adenosine triphosphate Pyrophosphate Guanosine triphosphate Neuronal Excitability Gq Signalling cascade