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

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
Effect of midodrine on chlorpromazine-induced orthostatic hypotension in rabbits: comparison with amezinium, etilefrine and droxidopa.	2000 Dec	11145175
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
Diabetes-induced changes in retinal NAD-redox status: pharmacological modulation and implications for pathogenesis of diabetic retinopathy.	2001	11287819
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
Effect of alpha-adrenoceptor agents on imipramine-induced antinociception in nerve-ligated mice.	2001 Apr	11313154
The short-term effects of terazosin in Japanese men with benign prostatic hyperplasia.	2001 Apr	11301364
Effect of KMD-3213, an alpha1A-adrenoceptor antagonist, on the prostatic urethral pressure and blood pressure in male decerebrate dogs.	2001 Apr	11260350
Effect of dexmedetomidine on the release of [3H]-noradrenaline from rat kidney cortex slices: characterization of alpha2-adrenoceptor.	2001 Apr	11137626
A61603-induced vasoconstriction in porcine carotid vasculature: involvement of a non-adrenergic mechanism.	2001 Apr 13	11334851
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
beta-Adrenergic stimulation synchronizes intracellular Ca(2+) release during excitation-contraction coupling in cardiac myocytes.	2001 Apr 27	11325871
Call for global snake-bite control and procurement funding.	2001 Apr 7	11303612
Cis- and trans-N-benzyl-octahydrobenzo[g]quinolines. Adrenergic and dopaminergic activity studies.	2001 Apr 9	11294383
Chronic vasodilation induces matrix metalloproteinase 9 (MMP-9) expression during microvascular remodeling in rat skeletal muscle.	2001 Feb	11296850
[A randomized comparative study assessing once versus twice a day treatment of benign prostatic hyperplasia with terazosin].	2001 Feb	11280890
Magnetic resonance imaging and morphometric histologic analysis of prostate tissue composition in predicting the clinical outcome of terazosin therapy in benign prostatic hyperplasia.	2001 Feb	11240824
Left ventricle and arteries: structure, function, hormones, and disease.	2001 Feb	11230298
The pancreatic islets in spontaneously hypertensive rats: islet blood flow and insulin production.	2001 Feb	11182754
Release of amines from acidified stores following accumulation by Transport-P.	2001 Feb	11181426
Overstimulation of the alpha1B-adrenergic receptor causes a "seizure plus" syndrome.	2001 Feb	11175818
Postjunctional alpha(2C)-adrenoceptor contractility in human saphenous vein.	2001 Feb 16	11226402
Unorthodox angiogenesis in skeletal muscle.	2001 Feb 16	11166277
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
Traceless solid-phase synthesis of 2,4-diaminoquinazolines.	2001 Feb 22	11178831
[The efficacy and safety of terazosin and tamsulosin in patients with urinary disturbance accompanying prostatic hypertrophy].	2001 Jan	11235215
A quantitative analysis of antagonism and inverse agonism at wild-type and constitutively active hamster alpha1B-adrenoceptors.	2001 Jan	11191834
Targeted transurethral microwave thermotherapy versus alpha-blockade in benign prostatic hyperplasia: outcomes at 18 months.	2001 Jan	11164146
A N-terminal PTHrP peptide fragment void of a PTH/PTHrP-receptor binding domain activates cardiac ET(A) receptors.	2001 Jan	11159691
alpha(1B) adrenergic receptors in gonadotrophin-releasing hormone neurones: relation to Transport-P.	2001 Jan	11156594
Combined effect of terazosin and finasteride on apoptosis, cell proliferation, and transforming growth factor-beta expression in benign prostatic hyperplasia.	2001 Jan 1	11170131
Amantadine-induced cortical myoclonus.	2001 Jan 23	11160978
Effect of carvedilol on atrioventricular conduction in the ischemic heart.	2001 Jan 26	11165226
Hemorrhage-induced alpha-adrenergic signaling results in myocardial TNF-alpha expression and contractile dysfunction.	2001 Jul	11406472
Vascular actions of MDMA involve alpha1 and alpha2-adrenoceptors in the anaesthetized rat.	2001 Jun	11375260
Noradrenaline modulates oyster hemocyte phagocytosis via a beta-adrenergic receptor-cAMP signaling pathway.	2001 Jun	11356037
Comparison of prazosin, terazosin and tamsulosin: functional and binding studies in isolated prostatic and vascular human tissues.	2001 Jun 1	11398170
Synthesis, biological evaluation, and pharmacophore generation of new pyridazinone derivatives with affinity toward alpha(1)- and alpha(2)-adrenoceptors.	2001 Jun 21	11405649
Structure-activity studies for a novel series of bicyclic substituted hexahydrobenz[e]isoindole alpha1A adrenoceptor antagonists as potential agents for the symptomatic treatment of benign prostatic hyperplasia.	2001 Jun 7	11384242
Enduring vulnerability to transient reinstatement of hemiplegia by prazosin after traumatic brain injury.	2001 Mar	11284550
Characterization of [3H]CGP 12177 binding to beta-adrenergic receptors in intact eel hepatocytes.	2001 Mar	11254364
Morphological and functional in vitro and in vivo characterization of the mouse corpus cavernosum.	2001 Mar	11250885
Nerve evoked P2X receptor contractions of rat mesenteric arteries; dependence on vessel size and lack of role of L-type calcium channels and calcium induced calcium release.	2001 Mar	11250870
Extracellular matrix proteins in cardiac fibroblasts derived from rat hearts with chronic pressure overload: effects of beta-receptor blockade.	2001 Mar	11181017
Effect of JTH-601, a putative alpha(1L)-adrenoceptor antagonist, on guinea pig nasal mucosa vasculature.	2001 Mar 23	11282123
Posttraining infusion of norepinephrine and corticotropin releasing factor into the bed nucleus of the stria terminalis enhanced retention in an inhibitory avoidance task.	2001 Mar 31	11403518
Evaluating adverse cardiovascular effects of drug treatment for benign prostatic hyperplasia (BPH): methodological considerations.	2001 May	11337216
Interaction of formamidine pesticides with the presynaptic alpha(2)-adrenoceptor regulating.	2001 May 1	11312645
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).

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