Description
Guanadrel is an adrenergic neuron blocker used for essential hypertension. Its mechanism
of action and side effects are similar to those of guanethidine.
Originator
Hylorel,Pennwalt,US,1983
Uses
Guanadrel is an adrenergic neuron blocker used for essential hypertension. The mechanism of action and side effects are similar to guanethidine.
It is used for treating hypertension in patients who do not respond to thiazide diuretics.
It can be used as an adjuvant drug in thiazide treatment for reaching an optimal level of
blood pressure.
Uses
It is used to treat hypertension in patients who do not adequately respond to thiazide
diuretics. It can be used as an adjuvant in thiazide treatment for reaching an optimal level
of blood pressure.
Definition
ChEBI: A spiroketal resulting from the formal condensation of the keto group of cyclohexanone with the hydroxy groups of 1-(2,3-dihydroxypropyl)guanidine. A postganglionic adrenergic blocking agent formerly used (generally as the sulfate salt) for the management
f hypertension, it has been largely superseded by other drugs less likely to cause orthostatic hypotension (dizzy spells on standing up or stretching).
Manufacturing Process
A mixture of 10.5 g of 1,4-dioxaspiro[4.5]decane-2-methylamine and 8.6 g of
2-methyl-2-thiopseudourea sulfate in 40 ml of water was heated on the steam
bath for 4 hours during which 2.0 g of methylmercaptan was collected in a dry
ice bath connected to the reaction flask through a water cooled reflux
condenser. The reaction mixture was then evaporated at 15 mm pressure to a
solid residue which was then dissolved in 80 ml of 50/50 methanol-ethanol.
The solution was filtered and evaporated to approximately 50 ml volume and
allowed to cool and crystallize, giving a crop melting at 213.5°C to 215°C of
1,4-dioxaspiro[4.5]decan-2-ylmethyl)-guanidine sulfate.
brand name
Hylorel (Pharmacia & Upjohn).
Therapeutic Function
Antihypertensive
Synthesis
Guanadrel, (1,4-dioxaspiro[4,5]dec-2-ylmethyl)guanidine (12.3.8), is synthesized when cyclohexanone undergoes ketalization by 3-chloro-1,2-proandiol, forming 2-
chloromethyl-1,4-dioxyspiro[4,5]decane (12.3.5), which is further akylated by sodium
phthalimide. After alkyline hydrazinolysis, the resulting phthalimide derivative (12.3.6) is
transformed into 2-aminomethyl-1,4-dioxyspiro[4,5]decane (12.3.7), which is reacted
with S-methylthiourea, giving the desired guanadrel (12.3.8) [80¨C82].
