Editing Reserpine (section)

==Mechanism of action==
{{See also|Monoamine-depleting agent}}

Reserpine irreversibly blocks the H<sup>+</sup>-coupled [[vesicular monoamine transporter]]s, [[VMAT1]] and [[VMAT2]]. [[VMAT1]] is mostly expressed in neuroendocrine cells. VMAT2 is mostly expressed in neurons. Thus, it is the blockade of neuronal VMAT2 by reserpine that inhibits uptake and reduces stores of the [[monoamine neurotransmitter]]s [[norepinephrine]], [[dopamine]], [[serotonin]] and [[histamine]] in the synaptic vesicles of neurons.<ref>{{cite journal | vauthors = Yaffe D, Forrest LR, Schuldiner S | title = The ins and outs of vesicular monoamine transporters | journal = The Journal of General Physiology | volume = 150 | issue = 5 | pages = 671–682 | date = May 2018 | pmid = 29666153 | pmc = 5940252 | doi = 10.1085/jgp.201711980 }}</ref> VMAT2 normally transports free intracellular norepinephrine, serotonin, and dopamine in the presynaptic nerve terminal into presynaptic vesicles for subsequent release into the [[synaptic cleft]] ("[[exocytosis]]"). Unprotected neurotransmitters are metabolized by [[monoamine oxidase|MAO]] (as well as by [[COMT]]), attached to the outer membrane of the mitochondria in the cytosol of the axon terminals, and consequently never excite the post-synaptic cell. Thus, reserpine increases removal of monoamine neurotransmitters from neurons, decreasing the size of the neurotransmitter pools, and thereby decreasing the amplitude of neurotransmitter release.<ref>{{cite journal | vauthors = Eiden LE, Weihe E | title = VMAT2: a dynamic regulator of brain monoaminergic neuronal function interacting with drugs of abuse | journal = Annals of the New York Academy of Sciences | volume = 1216 | issue = 1 | pages = 86–98 | date = January 2011 | pmid = 21272013 | pmc = 4183197 | doi = 10.1111/j.1749-6632.2010.05906.x | bibcode = 2011NYASA1216...86E }}</ref> As it may take the body days to weeks to replenish the depleted VMATs, reserpine's effects are long-lasting.<ref>{{cite journal | vauthors = German CL, Baladi MG, McFadden LM, Hanson GR, Fleckenstein AE | title = Regulation of the Dopamine and Vesicular Monoamine Transporters: Pharmacological Targets and Implications for Disease | journal = Pharmacological Reviews | volume = 67 | issue = 4 | pages = 1005–24 | date = October 2015 | pmid = 26408528 | pmc = 4630566 | doi = 10.1124/pr.114.010397 | doi-access = free }}</ref>