How is removal of NE?

Norepinephrine may: 1) diffuse out of the synaptic space and enter the general circulation, 2) be metabolized to O-methylated derivatives by postsynaptic cell membrane–associated catechol O-methyltransferase (COMT) in the synaptic space, 3) be recaptured by an uptake system that pumps the norepinephrine back into the neuron The uptake by the neuronal membrane involves a sodium/potassium-activated ATPase that can be inhibited by tricyclic antidepressants, such as imipramine, or by cocaine Uptake of norepinephrine into the presynaptic neuron is the primary mechanism for termination of norepinephrine’s effects