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.

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Guanethidine

Clinical data
AHFS/Drugs.com	Micromedex Detailed Consumer Information
MedlinePlus	a600027
ATC code	C02CC02 (WHO) S01EX01 (WHO)
Pharmacokinetic data
Elimination half-life	1.5 days
Identifiers
IUPAC name 2-[2-(azocan-1-yl)ethyl]guanidine
CAS Number	645-43-2 Y
PubChem CID	3518
IUPHAR/BPS	7194
DrugBank	DB01170 Y
ChemSpider	3398 Y
UNII	5UBY8Y002G
KEGG	D08030 N
ChEBI	CHEBI:5557 Y
ChEMBL	ChEMBL765 Y
CompTox Dashboard (EPA)	DTXSID5023116
ECHA InfoCard	100.000.220
Chemical and physical data
Formula	C10H22N4
Molar mass	198.314 g·mol−1
3D model (JSmol)	Interactive image
SMILES N(=C(\N)N)\CCN1CCCCCCC1
InChI InChI=1S/C10H22N4/c11-10(12)13-6-9-14-7-4-2-1-3-5-8-14/h1-9H2,(H4,11,12,13) Y Key:ACGDKVXYNVEAGU-UHFFFAOYSA-N Y
NY (what is this?)  (verify)

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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.

Intravenous nerve block (Bier block) using guanethidine has been used to treat chronic pain caused by complex regional pain syndrome.^[1]

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

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.