Guanadrel

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Guanadrel
Guanadrel.png
Names
IUPAC name
2-(1,4-Dioxaspiro[4.5]decan-2-ylmethyl)guanidine
Identifiers
40580-59-4 YesY
ChEBI CHEBI:5555 N
ChEMBL ChEMBL1037 N
ChemSpider 35305 N
Jmol-3D images Image
KEGG D08029 YesY
MeSH C004945
PubChem 38521
Properties
C10H19N3O2
Molar mass 213.28 g·mol−1
Except where noted otherwise, data is given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
 N verify (what isYesY/N?)
Infobox references

Guanadrel is an antihypertensive agent.[1] It is used in the form of its sulfate.

Mechanism of action[edit]

Guanadrel is a postganglionic adrenergic blocking agent. Uptake of guanadrel and storage in sympathetic neurons occurs via the norepinephrine pump; guanadrel slowly displaces norepinephrine from its storage in nerve endings and thereby blocks the release of norepinephrine normally produced by nerve stimulation. The reduction in neurotransmitter release in response to sympathetic nerve stimulation, as a result of catecholamine depletion, leads to reduced arteriolar vasoconstriction, especially the reflex increase in sympathetic tone that occurs with a change in position. Guanadrel is rapidly and well absorbed from gastrointestinal tract.[2]

In 1981 the JAMA reported guanadrel as an effective step II or step III treatment of hypertension.[3]

Chemistry[edit]

Guanadrel can be synthesized when cyclohexanone undergoes ketalization by 3-chloro-1,2-propanediol, forming 2-chloromethyl-1,4-dioxyspiro[4,5]decane, which is further reacted with sodium phthalimide.[4][5][6] After alkaline hydrazinolysis, the resulting phthalimide derivative is transformed into 2-aminomethyl-1,4-dioxyspiro[4,5]decane, which is reacted with S-methylthiourea, giving the desired guanadrel.

Guanadrel synthesis

References[edit]

  1. ^ Oren A, Rotmensch HH, Vlasses PH et al. (1985). "A dose-titration trial of guanadrel as step-two therapy in essential hypertension". J Clin Pharmacol 25 (5): 343–6. doi:10.1002/j.1552-4604.1985.tb02852.x. PMID 4031111. 
  2. ^ Guanadrel, from Pharmacogenetics Knowledge Base
  3. ^ M. I. Dunn and J. L. Dunlap (1981). "Guanadrel. A new antihypertensive drug". JAMA 245 (16): 1639–42. doi:10.1001/jama.1981.03310410017019. PMID 7206175. 
  4. ^ W.R. Hardie, J.E. Aaron, FR 1522153  (1968)
  5. ^ W.R. Hardie, J.E. Aaron, S. Afr. Pat. 67 06.328 (1968)
  6. ^ J.E. Aaron, W.R. Hardie, U.S. Patent 3,547,951 (1970)

External links[edit]