Guanethidine

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Guanethidine
Guanethidine.svg
Systematic (IUPAC) name
2-[2-(azocan-1-yl)ethyl]guanidine
Clinical data
AHFS/Drugs.com Micromedex Detailed Consumer Information
MedlinePlus a600027
Legal status ?
Pharmacokinetic data
Half-life 1.5 days
Identifiers
CAS number 645-43-2 YesY
ATC code C02CC02 S01EX01
PubChem CID 3518
DrugBank DB01170
ChemSpider 3398 YesY
UNII 5UBY8Y002G YesY
KEGG D08030 N
ChEBI CHEBI:5557 YesY
ChEMBL CHEMBL765 YesY
Chemical data
Formula C10H22N4 
Mol. mass 198.309 g/mol
 N (what is this?)  (verify)

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.

Side effects[edit]

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

Pharmacology[edit]

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.

Uses[edit]

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]

Chemical synthesis[edit]

Guanethidine is synthesized beginning with the alkylation of azocine with chloroacetonitrile. This reaction which forms 1-azocinylacetonitrile, which can be reduced into 1-(2-aminoethyl)azocine by using lithium aluminium hydride as a reductant. This compound reacts with S-methylthiourea forming guanethidine.[2][3][4]

Guanethidine synthesis.png

References[edit]

  1. ^ 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, table of contents. doi:10.1097/00000539-200211000-00045. PMID 12401623. 
  2. ^ R.P. Mull, U.S. Patent 2,928,829 (1960)
  3. ^ R.P. Mull, U.S. Patent 3,006,913 (1961)
  4. ^ R.P. Mull, U.S. Patent 3,055,882 (1962)