Guanadrel
Encyclopedia
Guanadrel is an antihypertensive agent. It is used in the form of its sulfate
.
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.
In 1981 the JAMA
reported guanadrel as an effective step II or step III treatment of hypertension.
undergoes ketalization by 3-chloro-1,2-proandiol, forming 2-chloromethyl-1,4-dioxyspiro[4,5]decane, which is further reacted with sodium phthalimide. 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.
Sulfate
In inorganic chemistry, a sulfate is a salt of sulfuric acid.-Chemical properties:...
.
Mechanism of action
Guanadrel is a postganglionic adrenergic blocking agent. Uptake of guanadrel and storage in sympathetic neurons occurs via the norepinephrineNorepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...
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
Catecholamine
Catecholamines are molecules that have a catechol nucleus consisting of benzene with two hydroxyl side groups and a side-chain amine. They include dopamine, as well as the "fight-or-flight" hormones adrenaline and noradrenaline released by the adrenal medulla of the adrenal glands in response to...
depletion, leads to reduced arteriolar vasoconstriction
Vasoconstriction
Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, particularly the large arteries, small arterioles and veins. The process is the opposite of vasodilation, the widening of blood vessels. The process is particularly important in...
, especially the reflex increase in sympathetic tone that occurs with a change in position. Guanadrel is rapidly and well absorbed from gastrointestinal tract.
In 1981 the JAMA
Jama
Jama or JAMA may refer to:* Jama Software, a privately held company in Portland, Oregon* Journal of the American Medical Association, an international peer-reviewed general medical journal...
reported guanadrel as an effective step II or step III treatment of hypertension.
Chemistry
Guanadrel, (1,4-dioxaspiro[4,5]dec-2-ylmethyl)guanidine, is synthesized when cyclohexanoneCyclohexanone
Cyclohexanone is the organic compound with the formula 5CO. The molecule consists of six-carbon cyclic molecule with a ketone functional group. This colorless oil has an odor reminiscent of peardrop sweets as well as acetone. Over time, samples assume a yellow color due to oxidation...
undergoes ketalization by 3-chloro-1,2-proandiol, forming 2-chloromethyl-1,4-dioxyspiro[4,5]decane, which is further reacted with sodium phthalimide. 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.
- W.R. Hardie, J.E. Aaron, (1968).
- W.R. Hardie, J.E. Aaron, S. Afr. Pat. 67 06.328 (1968).
- J.E. Aaron, W.R. Hardie, (1970).
External links
- webpage on guanadrel, from Mayo ClinicMayo ClinicMayo Clinic is a not-for-profit medical practice and medical research group specializing in treating difficult patients . Patients are referred to Mayo Clinic from across the U.S. and the world, and it is known for innovative and effective treatments. Mayo Clinic is known for being at the top of...