PRAZOSIN

Details

Stereochemistry	ACHIRAL
Molecular Formula	C19H21N5O4
Molecular Weight	383.4011
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=CC2=NC(=NC(N)=C2C=C1OC)N3CCN(CC3)C(=O)C4=CC=CO4

InChI

InChIKey=IENZQIKPVFGBNW-UHFFFAOYSA-N

InChI=1S/C19H21N5O4/c1-26-15-10-12-13(11-16(15)27-2)21-19(22-17(12)20)24-7-5-23(6-8-24)18(25)14-4-3-9-28-14/h3-4,9-11H,5-8H2,1-2H3,(H2,20,21,22)

HIDE SMILES / InChI

Molecular Formula	C19H21N5O4
Molecular Weight	383.4011
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/017442%20s043lbl.pdf

Prazosin (trade names Minipress, Vasoflex, Lentopres, and Hypovase) is a selective α-1-adrenergic receptor antagonist used to treat hypertension. Prazosin acts by inhibiting the postsynaptic alpha-1-adrenoceptors on vascular smooth muscle. This inhibits the vasoconstrictor effect of circulating and locally released catecholamines (epinephrine and norepinephrine), resulting in peripheral vasodilation. Prazosin is orally active and has a minimal effect on cardiac function due to its alpha-1 receptor selectivity. However, when prazosin is started, heart rate and contractility go up in order to maintain the pre-treatment blood pressures because the body has reached homeostasis at its abnormally high blood pressure. The blood pressure lowering effect becomes apparent when prazosin is taken for longer periods of time. The heart rate and contractility go back down over time and blood pressure decreases. The antihypertensive characteristics of prazosin make it a second-line choice for the treatment of high blood pressure. Prazosin is also useful in treating urinary hesitancy associated with prostatic hyperplasia, blocking alpha-1 receptors, which control constriction of both the prostate and urethra. Although not a first line choice for either hypertension or prostatic hyperplasia, it is a choice for patients who present with both problems concomitantly. Common (4–10% frequency) side effects of prazosin include dizziness, headache, drowsiness, lack of energy, weakness, palpitations, and nausea. Less frequent (1–4%) side effects include vomiting, diarrhea, constipation, edema, orthostatic hypotension, dyspnea, syncope, vertigo, depression, nervousness, and rash.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Adrenergic receptor alpha-1 169 Target ID: CHEMBL2094251 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9135028	Antagonist 2778	2.0 nM [Kd]
Alpha-1a adrenergic receptor 66 Target ID: CHEMBL229 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25557493	Antagonist 2778	0.04 nM [Ki]
Alpha-1b adrenergic receptor 44 Target ID: CHEMBL232 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9888842	Antagonist 2778	0.28 nM [Ki]
Alpha-1d adrenergic receptor 36 Target ID: CHEMBL223 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24365159	Antagonist 2778	0.42 nM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Hypertension 567 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/017442%20s043lbl.pdf	Primary	Approved 8429	MINIPRESS Approved Use Prazosin hydrochloride capsules are indicated in the treatment of hypertension. They can be used alone or in combination with other antihypertensive drugs such as diuretics or beta-adrenergic blocking agents. Launch Date 1976
Prostatic hyperplasia 4 Sources: https://clinicaltrials.gov/ct2/show/NCT00687388	Primary	Phase IV 63	MINIPRESS Approved Use Prazosin hydrochloride capsules are indicated in the treatment of hypertension. They can be used alone or in combination with other antihypertensive drugs such as diuretics or beta-adrenergic blocking agents. Launch Date 1976
Post-traumatic headache 2 Sources: https://clinicaltrials.gov/ct2/show/NCT02965027	Primary	Phase IV 63	MINIPRESS Approved Use Prazosin hydrochloride capsules are indicated in the treatment of hypertension. They can be used alone or in combination with other antihypertensive drugs such as diuretics or beta-adrenergic blocking agents. Launch Date 1976

C_max

Value	Dose	Co-administered	Analyte	Population
40 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7379445/	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:		PRAZOSIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
281 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7379445/	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:		PRAZOSIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
5.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7379445/	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:		PRAZOSIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
7.5% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7379445/	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:		PRAZOSIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
			inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OCT3 150 OCT1 512 OCT2 647

Drug as perpetrator

Target	Modality	Activity
OCT1 543	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/19833842/	yes [IC50 1.56 uM]
OCT3 150	inhibitor 3277 Sources: http://www.ncbi.nlm.nih.gov/pubmed/12110607	yes [IC50 12.6 uM]
OCT2 648	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/19833842/	yes [IC50 80.4 uM]

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://pubmed.ncbi.nlm.nih.gov/15098086/

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:8364	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:8364
MolPort	MolPort-000-891-036	https://www.molport.com/shop/molecule-link/MolPort-000-891-036
ZINC	ZINC000095616601	http://zinc15.docking.org/substances/ZINC000095616601
eMolecules	670703	https://www.emolecules.com/cgi-bin/more?vid=670703

PubMed

Title	Date	PubMed
Characterization of alpha1-adrenoceptor subtypes mediating noradrenaline-induced contraction of rat epididymal vas deferens in calcium-free medium.	1999	10416824
Human cloned alpha1A-adrenoceptor isoforms display alpha1L-adrenoceptor pharmacology in functional studies.	1999 Apr 16	10334511
Cocaine-induced hypertension: role of the peripheral sympathetic system.	1999 Aug	10433872
In vitro alpha1-adrenoceptor pharmacology of Ro 70-0004 and RS-100329, novel alpha1A-adrenoceptor selective antagonists.	1999 May	10369480
Characterization of human recombinant alpha(2A)-adrenoceptors expressed in Chinese hamster lung cells using intracellular Ca(2+) changes: evidence for cross-talk between recombinant alpha(2A)- and native alpha(1)-adrenoceptors.	2000 Apr	10742289
Are alpha-blockers involved in lower urinary tract dysfunction in multiple system atrophy? A comparison of prazosin and moxisylyte.	2000 Mar 15	10699651
Vasoconstrictive drugs increase carbonic anhydrase I in vascular smooth muscle while vasodilating drugs reduce the activity of this isozyme by a direct mechanism of action.	2001	11392054
Hypoxic-ischaemic brain damage in immature rats: effects of adrenoceptor modulation.	2001	11277361
Lower urinary tract symptoms suggestive of benign prostatic obstruction--Triumph: the role of general practice databases.	2001	11275742
Role of the alpha(1)- and alpha(2)-adrenoceptors of the paraventricular nucleus on the water and salt intake, renal excretion, and arterial pressure induced by angiotensin II injection into the medial septal area.	2001 Apr	11403985
Expression and functional characterization of the mt1 melatonin receptor from rat brain in Xenopus oocytes: evidence for coupling to the phosphoinositol pathway.	2001 Apr	11316324
Effect of the blood substitute diaspirin crosslinked hemoglobin in rat mesenteric and human radial collateral arteries.	2001 Apr	11300652
Determinants of terminal mesenteric artery resistance during the first postnatal month.	2001 Apr	11254494
Effect of dexmedetomidine on the release of [3H]-noradrenaline from rat kidney cortex slices: characterization of alpha2-adrenoceptor.	2001 Apr	11137626
Effects of brucine, a plant alkaloid, on M(1) muscarinic receptors and alpha(1)-adrenoceptors in the rabbit vas deferens preparation.	2001 Apr	11024498
Characterization of the catalytic cycle of ATP hydrolysis by human P-glycoprotein. The two ATP hydrolysis events in a single catalytic cycle are kinetically similar but affect different functional outcomes.	2001 Apr 13	11154703
Call for global snake-bite control and procurement funding.	2001 Apr 7	11303612
Chronic vasodilation induces matrix metalloproteinase 9 (MMP-9) expression during microvascular remodeling in rat skeletal muscle.	2001 Feb	11296850
Postjunctional alpha(2C)-adrenoceptor contractility in human saphenous vein.	2001 Feb 16	11226402
Neural mechanisms involved in the delay of gastric emptying and gastrointestinal transit of liquid after thoracic spinal cord transection in awake rats.	2001 Feb 20	11280307
Alpha2-adrenoceptor-mediated inhibition of cultured sympathetic neurons: changes in alpha2A/D-adrenoceptor-deficient mice.	2001 Jan	11191829
Sarcomere length-induced alterations of capillary hemodynamics in rat spinotrapezius muscle: vasoactive vs passive control.	2001 Jan	11162197
Simvastatin inhibits noradrenaline-induced hypertrophy of cultured neonatal rat cardiomyocytes.	2001 Jan	11156573
Antihypertensive monotherapy and cardiovascular responses to an acoustic startle stimulus.	2001 Jan	11152367
Reversal of Haemorrhagic Shock in Rats by Tetrahydroaminoacridine.	2001 Jan	11150921
Catecholamine responses to alpha-adrenergic blockade during exercise in women acutely exposed to altitude.	2001 Jan	11133901
In vivo demonstration of alpha(1A)-adrenoceptor subtype selectivity of KMD-3213 in rat tissues.	2001 Jan	11123376
Increased alpha(1)- and alpha(2)-adrenoceptor-mediated contractile responses of human skeletal muscle resistance arteries in chronic limb ischemia.	2001 Jan	11121814
Combined effect of terazosin and finasteride on apoptosis, cell proliferation, and transforming growth factor-beta expression in benign prostatic hyperplasia.	2001 Jan 1	11170131
Hemorrhage-induced alpha-adrenergic signaling results in myocardial TNF-alpha expression and contractile dysfunction.	2001 Jul	11406472
Comparison of prazosin, terazosin and tamsulosin: functional and binding studies in isolated prostatic and vascular human tissues.	2001 Jun 1	11398170
The role of several alpha(1)- and alpha(2)-adrenoceptor subtypes mediating vasoconstriction in the canine external carotid circulation.	2001 Mar	11250880
Low temperature prevents potentiation of norepinephrine release by phenylephrine.	2001 Mar	11099782
Initiation of nonselective alpha1-antagonist therapy and occurrence of hypotension-related adverse events among men with benign prostatic hyperplasia: a retrospective cohort study.	2001 May	11394731
Identification and localization of three photobinding sites of iodoarylazidoprazosin in hamster P-glycoprotein.	2001 May	11322883
Role of G(i)-proteins in norepinephrine-mediated vasoconstriction in rat tail artery smooth muscle.	2001 May 1	11301051

Patents

Sample Use Guides

In Vivo Use Guide

Initial: 1 mg PO q8-12hr Maintenance: 6-15 mg/day divided 2 or 3 times daily; alternatively, 1-5 mg PO BID; may increase dose to 20 mg/day in divided doses; some patients may benefit from up to 40 mg/day in divided doses

Route of Administration: Oral

In Vitro Use Guide

Both HEL and K562 cells, with a start cell number of 1×E4 cells/ml, were incubated in 24-well plates 2 or 3 days with different concentrations of the receptor subtype-specific adrenergic antagonists, prazosin in triplicates. All antagonists were obtained from Sigma Austria and were added to the culture medium dissolved in Aqua bidest. After the incubation period, proliferation and viability of the cells were measured with a CASY-1® Cell Counter and Analyzer (Schaerfe, Reutlingen, Germany).

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:15:36 GMT 2023` Edited by `admin` on `Fri Dec 15 15:15:36 GMT 2023`
Record UNII	XM03YJ541D
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

PRAZOSIN

Official Name

English

prazosin [INN]

Common Name

English

1-(4-AMINO-6,7-DIMETHOXYQUINAZOLIN-2-YL)-4-(FURAN-2-YLCARBONYL)PIPERAZINE

Systematic Name

English

CP-122991

Code

English

TERAZOSIN HYDROCHLORIDE DIHYDRATE IMPURITY K [EP IMPURITY]

Common Name

English

PRAZOSIN [VANDF]

Common Name

English

PRAZOSIN [MI]

Common Name

English

Prazosin [WHO-DD]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29713