adrenergic neuron blocker
An adrenergic neuron blocker quiets the sympathetic system by attacking the supply, not the receiver. Rather than blocking the adrenergic receptor like a beta or alpha blocker, it acts inside the nerve terminal to stop norepinephrine from being released in the first place, so the message is never sent.
These drugs are taken up into the sympathetic nerve ending by the same transporter that normally recaptures norepinephrine. Once inside, guanethidine prevents the vesicles from releasing their transmitter, while reserpine depletes the vesicle stores by blocking the pump that fills them, so the terminal gradually runs dry. The net effect is reduced sympathetic transmission and lower blood pressure.
Historically these were important antihypertensives, but they have fallen out of routine use because of troublesome effects: severe postural drop in blood pressure, sexual dysfunction, and, with reserpine, depression from depleting brain monoamines as well. They survive mainly in the classroom and in rare niche situations.
Reserpine, derived from the Indian snakeroot plant, lowers blood pressure by depleting norepinephrine from sympathetic nerve terminals over days.
A classic norepinephrine-depleting drug.
Because guanethidine relies on the norepinephrine reuptake transporter to enter the nerve, drugs that block that transporter, such as tricyclic antidepressants, can prevent it from working, a classic teaching example of a drug interaction.