Once guanethidine has entered the nerve, it is concentrated in transmitter vesicles, where it replaces norepinephrine.

Guanethidine was once a mainstay for hypertension resistant to other agents, and was often used safely during pregnancy, but it is no longer used in the US due to lack of availability.

It is still licensed in some countries, e.g., UK, for the rapid control of blood pressure in a hypertensive emergency.

[1] Side effects include postural and exercise hypotension, sexual dysfunction (delayed or retrograde ejaculation), and diarrhea.

Once inside the terminal it blocks the release of norepinephrine in response to arrival of an action potential.