Estulic,Sandoz,Switz.,1980
Antihypertensor;Alpha 2A agonist
Centrally acting a-adrenoceptor agonist. Antihypertensive
Guanfacine hydrochloride may be used as a pharmaceutical reference standard for the determination of the analyte in bulk drug and pharmaceutical formulations by spectrophotometry and high performance liquid chromatography.
ChEBI: Guanfacine hydrochloride is a member of acetamides. It has a role as a geroprotector.
2,6-Dichlorophenyl-acetyl-guanidine: A solution of 3.245 g (0.055 mol) of
guanidine in isopropanol is added to a solution of 11.7 g (0.05 mol) of 2,6-
dichlorophenyl-acetic acid ethyl ester (BP 142°C to 143°C/12 mm of Hg) in
20cc of isopropanol. The reaction mixture is allowed to stand overnight and is
subsequently concentrated by evaporation. After recrystallizing the residue
from methanol/ether 2,6-dichlorophenyl-acetyl-guanidine is obtained in the
form of white grains having a MP of 225°C to 227°C.
2,6-Dichlorophenyl-acetyl-guanidine hydrochloride: A solution of 5.6 g (0.025
mol) of 2,-dichlorophenylacetic acid chloride (BP 137°C to 138°C/12 mm of
Hg) in 10 cc of toluene is added dropwise to a mixture of 4.5 g (0.076 mol) of
guanidine and 60 cc of toluene. The reaction mixture is allowed to stand at
room temperature for 20 minutes, is then heated on a steam bath for 2 hours
and is subsequently cooled. The resulting precipitate is filtered off and washed
twice with 25 cc amounts of water in order to separate the guanidine
hydrochloride. The residue (2,6-dichlorophenyl-acetyl-guanidine) is washed
with chloroform for further purification and is then dissolved in 50 cc of
isopropanol. The pH-value of the solution is adjusted to 6 with ethanolic
hydrochloric acid and the solution is cooled. The resulting white needles are
again washed with chloroform. The resulting 2.6-dichlorophenyl-acetylguanidine hydrochloride has a MP of 213°C to 216°C.
Guanfacine hydrochloride,N-(aminoiminomethyl)-2,6-dichlorobenzeneacetamide(Tenex), is structurally related to clonidine hydrochloride andguanabenz acetate and shares many of their pharmacologicalproperties. The drug has a longer duration of action than eitherclonidine hydrochloride or guanabenz acetate. It lasts upto 24 hours. It also requires much longer (8–12 hours) for apeak effect to occur after the drug is administered.
Selective α 2A -adrenoceptor agonist (K d = 31 nM). Displays 60-fold selectivity over α 2B -adrenoceptors. Also available as part of the α 2 -Adrenoceptor Tocriset™ .
α-2 noradrenergic receptor agonist.
The pharmacokinetic properties for guanfacine differ from those of clonidine, guanabenz, and α-methyldopa. At pH 7.4,
guanfacine is predominately (67%) in the nonionized, lipid-soluble base form, which accounts for its high oral
bioavailability (>80%). Following an oral dose, peak plasma concentrations occur in 1 to 4 hours, with a relatively long
elimination half-life of 14 to 23 hours. The maximum blood pressure response occurs in 8 to 12 hours after oral
administration and is maintained up to 36 hours following its discontinuation. Following IV dosing, guanfacine achieves
the highest concentrations in liver and kidney, with low concentrations in the brain. Guanfacine is 64% bound to
plasma proteins. In patients with hepatic or renal impairment, its elimination half-life may be prolonged.
Guanfacine is metabolized principally by hepatic hydroxylation to its inactive metabolite, 3-hydroxyguanfacine (20%),
which is eliminated in the urine as its glucuronide (30%), sulfate (8%), or mercapturic acid conjugate (10%), and 24 to
37% is excreted as unchanged guanfacine. Its nearly complete bioavailability suggests no evidence of any
first-pass effect. Guanfacine and its inactive metabolites are excreted principally in urine, with approximately 80% of its
oral dose excreted in urine within 48 hours.
Overall, the therapeutic applications for guanfacine are similar to those of the other centrally acting α2-adrenergic
agonists and methyldopa. It has been effective as monotherapy in the treatment of patients with mild to moderate
hypertension. One advantage for guanfacine is its once-a-day dosing schedule. The use of diuretics to prevent
accumulation of fluid may allow a reduction in the dosage for guanfacine.
Overall, although the frequency of troublesome adverse effects produced by guanfacine is similar to that produced by
clonidine and the other centrally acting sympatholytics, their incidence and severity are lower with guanfacine. Unlike
clonidine, abrupt discontinuation of guanfacine rarely results in rebound hypertension. When a withdrawal syndrome
has occurred, its onset was slower and its symptoms less severe than the syndrome observed with clonidine.
[1] Patent: US2018/230105, 2018, A1. Location in patent: Paragraph 0538; 0539
