GUANFACINE HCL Property

Melting point:

215-217℃

RTECS 

CY1481000

storage temp. 

Inert atmosphere,Room Temperature

solubility 

H₂O: 12 mg/mL at 60 °C, soluble

form 

Solid

color 

white

Merck 

14,4561

Stability:

Hygroscopic

InChIKey

DGFYECXYGUIODH-UHFFFAOYSA-N

CAS DataBase Reference

29110-48-3(CAS DataBase Reference)

Safety

RIDADR 

3249

WGK Germany 

3

HazardClass 

6.1(b)

PackingGroup 

III

HS Code 

2925294500

Toxicity

LD50 in mice: 165 mg/kg orally (Coward)

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Danger

Hazard statements

H301Toxic if swalloed

Precautionary statements

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

P270Do not eat, drink or smoke when using this product.

P321Specific treatment (see … on this label).

P405Store locked up.

GUANFACINE HCL Chemical Properties,Usage,Production

Originator

Estulic,Sandoz,Switz.,1980

Uses

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.

Uses

Antihypertensor;Alpha 2A agonist

Uses

Centrally acting a-adrenoceptor agonist. Antihypertensive

Definition

ChEBI: Guanfacine hydrochloride is a member of acetamides. It has a role as a geroprotector.

Manufacturing Process

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.

brand name

Tenex (Dr. Reddy’s).

Therapeutic Function

Antihypertensive

General Description

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.

Biological Activity

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™ .

Biochem/physiol Actions

α-2 noradrenergic receptor agonist.

Pharmacokinetics

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.

Clinical Use

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.

Side effects

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.

storage

Store at RT