645-43-2 Usage
Description
Guanethidine Sulfate is an antihypertensive compound that functions by competing with norepinephrine for transport into presynaptic terminals of adrenergic neurons via the norepinephrine transporter. Once inside the nerve, it becomes concentrated in synaptic vesicles, depleting endogenous norepinephrine and reducing its release in response to action potentials. Its effects are limited to peripheral nerve terminals due to the inability of its basic guanidine group to cross the blood-brain barrier. Guanethidine Sulfate has also been explored for its potential in relieving chronic pain associated with complex regional pain syndrome.
Uses
Used in Pharmaceutical Industry:
Guanethidine Sulfate is used as an antihypertensive agent for the treatment of high blood pressure. It helps in reducing the release of norepinephrine, thereby lowering blood pressure.
Used in Ophthalmology:
Guanethidine Sulfate is used as an antiglaucoma agent for the management of elevated intraocular pressure. Its action in reducing norepinephrine release helps in lowering the pressure within the eye, providing relief to patients with glaucoma.
Used in Pain Management:
Guanethidine Sulfate is used as a therapeutic agent for the relief of chronic pain caused by complex regional pain syndrome. Its mechanism of action in reducing norepinephrine release may contribute to alleviating pain symptoms in these patients.
Therapeutic Function
Antihypertensive
Mechanism of action
Guanethidine is an adrenergic neuronal blocking agent that produces a selective block of peripheral sympathetic
pathways by replacing and depleting norepinephrine stores from adrenergic nerve endings, but not from the adrenal
medulla. It prevents the release of norepinephrine from adrenergic nerve endings in response to sympathetic
nerve stimulation. The chronic administration of guanethidine results in an increased sensitivity of these effector cells
to catecholamines. Following the oral administration of usual doses of guanethidine, depletion of the catecholamine
stores from adrenergic nerve endings occurs at a very slow rate, producing a more gradual and prolonged fall in
systolic blood pressure than in diastolic pressure. Associated with the decrease in blood pressure is an increase in
sodium and water retention and expansion of plasma volume (edema). If a diuretic is not administered concurrently with
guanethidine, tolerance to the antihypertensive effect of the guanethidine during prolonged therapy can result.
Pharmacokinetics
Guanethidine is incompletely absorbed from the GI tract and is metabolized in the liver to several metabolites,
including guanethidine N-oxide (from flavin mononucleotide). These metabolites of guanethidine are excreted in the
urine and have less than 10% of its hypotensive activity. The amount of drug that reaches the systemic circulation
after oral administration is highly variable from patient to patient and may range from 3 to 50% of a dose. Guanethidine
accumulates in the neurons with an elimination half-life of 5 days.
Clinical Use
Guanethidine monosulfate is metabolized by microsomalenzymes to 2-(6-carboxyhexylamino)ethylguanidine andguanethidine N-oxide . Both metabolites havevery weak antihypertensive properties. Guanethidine monosulfateis taken up by the amine pump located on theneuronal membrane and retained in the nerve, displacingnorepinephrine from its storage sites in the neuronal granules.The displaced norepinephrine is metabolized to homovanillicacid by mitochondrial MAO, depleting the nerveending of the neurotransmitter. The usefulness of guanethidinemonosulfate also resides in the fact that once it is takenup by the nerve, it produces a sympathetic blockade by inhibitingrelease of nonepinephrine that would occur on neuronalmembrane response to stimulation29 by the nerveaction potential. Guanethidine monosulfate stored in thegranules is released by the nerve action potential but hasvery low intrinsic activity for the adrenergic receptors on thepostjunctional membrane. Moderate doses for a prolongedperiod or large doses may produce undesirable side effectsby causing neuromuscular blockade and adrenergic nerveconduction blockade.
Side effects
Adverse effects of guanethidine frequently are dose related, including dizziness, weakness, lassitude, and syncope
resulting from postural or postexercise hypotension. A hot environment (i.e., a hot bath) may aggravate postural
hypotension. Patients should be warned about possible orthostatic hypotension and about the effect of rapid postural
changes on blood pressure (e.g., arising in the morning) that may cause fainting, especially during the initial period of
dosage adjustment. Sodium retention (edema) usually is controlled by the coadministration of a diuretic.
Drug interactions
Diuretics and other hypotensive drugs can potentiate the hypotensive effects of guanethidine. Reportedly, MAO
inhibitors antagonize the hypotensive effect of guanethidine. Oral sympathomimetic, nasal decongestants, and other
vasopressor agents should be used cautiously in patients receiving guanethidine, because guanethidine may
potentiate their pressor effects. The mydriatic response to ophthalmic administration of phenylephrine is markedly
increased in patients receiving guanethidine either ophthalmically or orally.
Tricyclic antidepressants and some phenothiazines block the uptake of guanethidine into adrenergic neurons and,
thus, prevent the hypotensive activity of guanethidine. Orthostatic hypotension may be increased by concomitant
administration of alcohol with guanethidine, and patients receiving guanethidine should be cautioned to limit alcohol
intake.
Check Digit Verification of cas no
The CAS Registry Mumber 645-43-2 includes 6 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 3 digits, 6,4 and 5 respectively; the second part has 2 digits, 4 and 3 respectively.
Calculate Digit Verification of CAS Registry Number 645-43:
(5*6)+(4*4)+(3*5)+(2*4)+(1*3)=72
72 % 10 = 2
So 645-43-2 is a valid CAS Registry Number.
InChI:InChI=1/C10H22N4.H2O4S/c11-10(12)13-6-9-14-7-4-2-1-3-5-8-14;1-5(2,3)4/h1-9H2,(H4,11,12,13);(H2,1,2,3,4)