|AHFS/Drugs.com||Micromedex Detailed Consumer Information|
|Elimination half-life||1.5 days|
|CompTox Dashboard (EPA)|
|Chemical and physical data|
|Molar mass||198.314 g·mol−1|
|3D model (JSmol)|
|(what is this?)|
Guanethidine is an antihypertensive drug that reduces the release of catecholamines, such as norepinephrine. Guanethidine is transported across the sympathetic nerve membrane by the same mechanism that transports norepinephrine itself (NET, uptake 1), and uptake is essential for the drug's action. Once guanethidine has entered the nerve, it is concentrated in transmitter vesicles, where it replaces norepinephrine. It may also inhibit the release of granules by decreasing norepinephrine.
Guanethidine is transported by uptake 1 into the presynaptic terminal transported by norepinephrine transporter (NET). (In this it competes with norepinephrine so can potentiate exogenously applied norepinephrine.) It becomes concentrated in norepinephrine transmitter vesicles, replacing norepinephrine in these vesicles. This leads to a gradual depletion of norepinephrine stores in the nerve endings. Once inside the terminal it blocks the release of norepinephrine in response to arrival of an action potential. Spontaneous release is not affected.
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.
Experimentally, guanethidine has been used in chemical sympathectomy in the research fields of neurophysiology and pharmacology. Daily injected with guanethidine into newborn rats causes irreversible destruction of the sympathetic ganglia and nerves.  
- Joyce PI, Rizzi D, Caló G, Rowbotham DJ, Lambert DG (November 2002). "The effect of guanethidine and local anesthetics on the electrically stimulated mouse vas deferens". Anesth. Analg. 95 (5): 1339–43. doi:10.1097/00000539-200211000-00045. PMID 12401623.
- Eränkö O, Eränkö L (November 1971). "Histochemical evidence of chemical sympathectomy by guanethidine in newborn rats". Histochem. J. 3 (6): 451–6. doi:10.1007/BF01014783. PMID 5158988.
- Augustyniak RA, Picken MM, Leonard D, Zhou XJ, Zhang W, Victor RG (January 2010). "Sympathetic nerves and the progression of chronic kidney disease during 5/6 nephrectomy: studies in sympathectomized rats". Clin. Exp. Pharmacol. Physiol. 37 (1): 12–8. doi:10.1111/j.1440-1681.2009.05253. PMID 19566818.