Originator
Regitine, Ciba, US ,1952
Definition
ChEBI: A substituted aniline that is 3-aminophenol in which the hydrogens of the amino group are replaced by 4-methylphenyl and 4,5-dihydro-1H-imidazol-2-ylmethyl groups respectively. An alpha-adrenergic antagonist, it is used fo
the treatment of hypertension.
Indications
Human erectile tissue has a population of membrane
receptors that are predominantly of the -adrenoceptor
subtype. Phentolamine (Vasomax) is a nonselective -
adrenoceptor blocking agent (see Chapter 11), and like
other such agents, it has been used to treat ED.
Nonselective adrenoceptor antagonists may provoke a
reflex that increases both sympathetic outflow and the
release of norepinephrine.
Manufacturing Process
199.24 parts of N-(p-methylphenyl)-m'-hydroxyphenylamine and 77.52 parts of 2-chloromethylimidazoline hydrochloride are heated for sixteen hours in an oil bath having a temperature of 150°C, while stirring and introducing a current of nitrogen. The viscous contents of the flask are then cooled to about 100°C, mixed with 400 parts by volume of hot water, and stirred for a short time.
After further cooling to about 60°C, 200 parts by volume of water and 500 parts by volume of ethyl acetate at 60°C are added, and the aqueous layer is separated. The excess of starting material may be recovered from the ethyl acetate.
The aqueous portion is chilled in a cooling chamber at -10°C, whereupon the hydrochloride of 2-[N-(p-methylphenyl)-N-(m'-hydroxyphenyl)-aminomethyl]imidazoline crystallizes. Upon being concentrated and cooled the mother liquor yields a further quantity of the hydrochloride. The combined quantities of hydrochloride are treated with a small quantity of cold water, dried with care, and washed with ethyl acetate. The product is then crystallized from a mixture of alcohol and ethyl acetate, and there is obtained a hydrochloride melting at 239°-240°C.
Brand name
Regitine
(Novartis) [Name previously used: Phentolamine Methanesulfonate.].
Therapeutic Function
Adrenergic blocker
General Description
Phentolamine isthe more effectiveα -blocker.
Mechanism of action
Its mechanism of action is as an α-adrenergic antagonist of both α1- and α2-receptors, causing vasodilation and reduction in peripheral resistance. When administered by intracavernosal injection, it is thought to cause relaxation of the cavernous smooth muscles and vasodilation of the penile arteries. This results in increased arterial blood flow into the corpus cavernosa as well as swelling and elongation of the penis. Venous outflow also is reduced, possibly as a result of increased venous resistance. Phentolamine is slowly released into venous circulation with minimal, if any, systemic effects. Time to peak effect is within 10 minutes, and duration of action when used with papaverine is 1 to 6 hours.
Side effects
Side effects of phentolamine are dose related. It
may cause orthostatic hypotension, reflex tachycardia,
cardiac arrhythmias, and rarely, myocardial infarction.
Phentolamine also may reduce sperm motility in vitro.
Safety Profile
Poison by subcutaneous, intravenous, and intraperitoneal routes. Moderately toxic by ingestion. Experimental reproductive effects. When heated to decomposition it emits toxic fumes of NOx.
Synthesis
Phentolamine, 2-[[N-(3??-hydroxyphenyl)-para-toluidion]methyl]-2-
imidazoline (12.2.8), is synthesized by alkylation of 3-(4-methylanilino)phenol using
2-chloromethylimidazoline [36, 37].
