Vesicular monoamine transporter 1 (SLC18A1) (VMAT1)

Vesicular monoamine transporter 1 (VMAT1) is a proton-coupled antiporter in the SLC18 family that uses the vesicular H+-electrochemical gradient to package monoamines—such as norepinephrine, epinephrine, dopamine, serotonin, and, to a lesser extent than VMAT2, histamine—into large dense-core secretory vesicles, predominantly in neuroendocrine cells including chromaffin and enterochromaffin cells[5][1][7]. VMAT1 exchanges two protons for each monoamine transported and operates via conformational changes driven by protonation of key residues; inhibitors include reserpine (competitive) and tetrabenazine-class compounds (generally noncompetitive, with much lower potency at VMAT1 than VMAT2)[1][5]. The gene encoding VMAT1 is SLC18A1, and genetic variation in SLC18A1 has been linked to susceptibility to schizophrenia and bipolar disorder I, highlighting a role for VMAT1 in neuropsychiatric disease biology[3]. VMAT1 is considered a valid therapeutic target conceptually within the VMAT family, although most approved drugs clinically modulate VMAT2 rather than VMAT1[6][3].

Other names

Solute carrier family 18 member A1 (SLC18A1)Chromaffin granule amine transporterVesicular amine transporter 1

Competitive inhibition at monoamine binding site (e.g., reserpine); Noncompetitive/allosteric inhibition reducing transporter activity (e.g., tetrabenazine-class, ketanserin)