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Chromaffin granule amine transporter Sodium- dependent serotonin transporter Trace amine- associated receptor 1 Sodium- dependent serotonin transporter Trace amine- associated receptor 1 5- hydroxytryptamine receptor 2A Sodium- dependent serotonin transporter Amine oxidase [flavin- containing] A Synaptic vesicular amine transporter Sodium- dependent serotonin transporter Aromatic-L- amino-acid decarboxylase Tryptophan 5-hydroxylase 1 Methamphetamine Methamphetamine Methamphetamine Methamphetamine Serotonin Serotonin Serotonin Serotonin Methamphetamine Methamphetamine 5-Hydroxy-L- tryptophan CO2 L-Tryptophan Tetrahydrobiopterin O2 4a- Hydroxytetrahydrobiopterin H2O O2 5- Hydroxyindoleacetic acid H2O2 NH3 FAD Pyridoxal 5'-phosphate Intestinal Serotonin pathway Gq Signalling cascade Fe2+ Serotonin Internalization Synaptic Vesicle Methamphetamine activates Trace amine-associated receptors which causes internalization of serotonin reuptake transporters. This prevents the reuptake of serotonin from the synapse. Serotonin accumulates in the synapse from the reversal and inhibition of serotonin transporters. Presynaptic Neuron Intestine Smooth Muscle Methamphetamine enters the synaptic vesicles through VMAT2 and inhibits VMAT2 and displaces the norepinephrine in the vesicles causing serotonin to spew out into the cytosol Serotonin is produced in the raphe nuclei and then stored in presynaptic vesicles Methamphetamine enters the nerve terminal via the serotonin reuptake transporter or by diffusing through the membrane Methamphetamine inhibits sodium-dependent serotonin receptors, by being a negative modulator. This prevents the reuptake of serotonin from the synapse. Cytosol In high doses methamphetamine inhibits Amine oxidase [flavin containing] A. The inhibition of MAO A which prevents the metabolic degradation of serotonin, and therefore increases the concentration of serotonin in the cytosol. Reversal of transport The high concentration of serotonin activates 5-hydroxytryptamine receptor 2A, 3A, and 3B which are mainly located in the gastrointestinal tract. Here it contracts smooth muscles causing food and toxins to pass through the intestine more quickly. The high concentration of serotonin activates 5-hydroxytryptamine receptor 2A, 3A, and 3B in the brain where the exact mechanisms are unknown. It is suspected to influence mood, perception, and cognition. Mood Postsynaptic Neuron The function of Trace amine-associated receptors with serotonin has only been observed in mRNA expression. Perception Cognition Diffusion
SLC18A1 SLC6A4 TAAR1 SLC6A4 TAAR1 HTR2A SLC6A4 MAOA SLC18A2 SLC6A4 DDC TPH1 Methamphetamine Methamphetamine Methamphetamine Methamphetamine Serotonin Serotonin Serotonin Serotonin Methamphetamine Methamphetamine 5-Hydroxy-L- tryptophan Carbon dioxide L-Tryptophan Tetrahydrobiopterin Oxygen 4a- Hydroxytetrahydrobiopterin Water Oxygen 5- Hydroxyindoleacetic acid Hydrogen peroxide Ammonia Intestinal Serotonin pathway Gq Signalling cascade
SLC18A1 SLC6A4 TAAR1 SLC6A4 TAAR1 HTR2A SLC6A4 MAOA SLC18A2 SLC6A4 DDC TPH1 Ice Ice Ice Ice 5-HT 5-HT 5-HT 5-HT Ice Ice