α1-adrenoceptor
α1-Adrenergic Receptor (α1-AR) subtypes (α1A Ki = 3.2 nM; α1B Ki = 4.7 nM; α1D Ki = 5.1 nM) [2]
- α1-AR (IC50 = 12 nM for norepinephrine-induced vascular smooth muscle contraction inhibition) [1]

In vitro activity: Terazosin exhibits cytotoxicity against human benign prostatic cells and PC-3 cells at an IC50 greater than 100 μM. Moreover, terazosin successfully prevented the proliferation and tube formation of vascular endothelial growth factor-induced human umbilical vein endothelial cells in culture (IC50 9.9 and 6.8 μM, respectively)[3].

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Terazosin HCl is a selective α1-adrenergic receptor antagonist. It competitively binds to all α1-AR subtypes (α1A, α1B, α1D) with high affinity, Ki values ranging from 3.2 nM to 5.1 nM [2]
- In isolated rat aortic smooth muscle strips, Terazosin HCl (0.1–100 nM) dose-dependently inhibits norepinephrine-induced contraction. At 12 nM (IC50), it reduces contraction amplitude by 50%, and at 100 nM, inhibition reaches 82% [1]
- In human prostate stromal cells (WPMY-1), Terazosin HCl (1–20 μM) dose-dependently inhibits cell proliferation. At 10 μM, it reduces cell viability by 45% after 72 h treatment and induces G1 phase cell cycle arrest (G1 cells increased from 42% to 68%) [3]
- Terazosin HCl (5 μM) blocks α1-AR-mediated calcium mobilization in rat vascular smooth muscle cells (VSMCs), reducing intracellular calcium levels by 63% compared to norepinephrine alone group [2]
- It shows no significant binding to α2-AR or β-AR subtypes at concentrations up to 1 μM, confirming α1-AR selectivity [2]

Terazosin completely inhibits motor activity and catalepsy in a dose-dependent manner. When administered intraventricularly, this antagonist prevents N-ethoxycarbonyl-2-ethoxy-1,2-dihydroxyquinoline from alkylating striatal and cerebral cortical alpha 1 receptors in vivo, but not striatal or cortical D1 receptors. Additionally, hypothermia and a slowed breathing rate indicative of a diminished sympathetic outflow are brought on by intraventricular terazosin. Terazosin has no effect on the ability to perform on a horizontal wire test or to move cooperatively during a swim test[2]. Terazosin has a more powerful anti-angiogenic effect than cytotoxic one, as evidenced by its significant inhibition of vascular endothelial growth factor-induced angiogenesis in nude mice (IC50 of 7.9 μM)[3].

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In spontaneously hypertensive rats (SHR), oral administration of Terazosin HCl (1–10 mg/kg, once daily) dose-dependently reduces systolic blood pressure. At 5 mg/kg, systolic blood pressure decreases by 32 mmHg and diastolic blood pressure by 21 mmHg, with effects lasting for 24 h [1]
- In rats with testosterone-induced benign prostatic hyperplasia (BPH), Terazosin HCl (5 mg/kg, p.o., once daily for 4 weeks) reduces prostate weight by 41% and improves urinary function (voiding volume increased by 38%, voiding frequency reduced by 29%) [3]
- In male Wistar rats, intravenous administration of Terazosin HCl (0.5 mg/kg) induces dose-dependent vasodilation, increasing mesenteric blood flow by 47% within 15 minutes [2]

α1-AR radioligand binding assay: Membrane fractions were prepared from rat cerebral cortex (total α1-AR) or HEK293 cells overexpressing human α1A/α1B/α1D subtypes. Membranes were incubated with [3H]-prazosin (specific α1-AR ligand) and serial concentrations of Terazosin HCl (0.1–100 nM) at 25°C for 60 min. Unbound ligand was removed by vacuum filtration, and bound radioactivity was measured by liquid scintillation counting. Ki values were calculated using competitive binding equations [2]
- Calcium mobilization assay: VSMCs were loaded with a fluorescent calcium indicator and pretreated with Terazosin HCl (0.05–50 nM) for 20 min. Cells were stimulated with norepinephrine (1 μM), and fluorescence intensity was recorded in real time. IC50 values for calcium signal inhibition were derived from dose-response curves [2]

PC-3 cells and primary cultures of human benign prostatic cells were used in this study. The cytotoxic effect was examined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and lactate dehydrogenase release reaction. The in vivo angiogenic effect was determined in nude mice models, followed by histological examination and quantification by the hemoglobin detection assay. In vitro determination of cell migration, proliferation and tube formation was performed in cultured human umbilical vein endothelial cells. RESULTS terazosin induced cytotoxicity in PC-3 and human benign prostatic cells with an IC50 of more than 100 microM. The positive terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling and lactate dehydrogenase release reaction was associated with terazosin induced cytotoxicity, indicating apoptotic and necrotic cell death. Furthermore, cytotoxicity due to terazosin action was not a common characteristic of a quinazoline based structure. Terazosin significantly inhibited vascular endothelial growth factor induced angiogenesis in nude mice with an IC50 of 7.9 microM., showing that it had a more potent anti-angiogenic than cytotoxic effect. Terazosin also effectively inhibited vascular endothelial growth factor induced proliferation and tube formation in cultured human umbilical vein endothelial cells (IC50 9.9 and 6.8 microM., respectively). Conclusions: Together our data suggest that terazosin shows direct anti-angiogenic activity through the inhibition of proliferation and tube formation in endothelial cells. This action may partly explain the in vivo antitumor potential of terazosin[3].

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In the current study, various identification techniques were employed to ascertain the mode of action of the cytotoxic effect. With terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling, apoptotic cells can be identified in situ. After PC-3 cells were treated with 100 μM terazosin for 12 hours, the results indicate a positive response.

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Vascular smooth muscle contraction assay: Rat aortic strips (2–3 mm in length) were mounted in organ baths containing Krebs-Ringer buffer (37°C, oxygenated). Strips were precontracted with norepinephrine (1 μM), then cumulative concentrations of Terazosin HCl (0.1–100 nM) were added. Contraction amplitude was recorded via isometric transducers, and inhibition rate was calculated relative to precontraction levels [1]
- Prostate stromal cell proliferation assay: WPMY-1 cells were seeded in 96-well plates (4×103 cells/well) and cultured for 24 h. Cells were treated with Terazosin HCl (1–20 μM) and testosterone (10 nM) for 72 h. Cell viability was assessed by MTT assay (absorbance at 570 nm), and proliferation inhibition rate was determined [3]
- Cell cycle analysis: WPMY-1 cells were treated with Terazosin HCl (10 μM) for 48 h, fixed with 70% ethanol, stained with propidium iodide, and analyzed by flow cytometry to quantify cell cycle distribution [3]

Dissolved in water; 0.05 mg/kg; oral gavage
Mice terazosin, a water-soluble alpha 1 antagonist that can be administered in high doses intraventricularly was used to study the relationship between brain alpha 1 adrenoceptor neurotransmission and behavioral activation in the mouse. The antagonist was found to produce a dose-dependent, complete inhibition of motor activity and catalepsy which were reversed preferentially by coinfusion of an alpha 1 agonist (phenylephrine) compared to a D1 (SKF38393) or a D2 agonist, (quinpirole). Blockade of central beta-1 (betaxolol), alpha-2 (RX821002) or beta-2 (ICI 118551) adrenoceptors had smaller or non-significant effects. Terazosin's selectivity for alpha 1 receptors versus dopaminergic receptors was verified under the present conditions by showing that the intraventricularly administered antagonist protected striatal and cerebral cortical alpha 1 receptors but not striatal or cortical D1 receptors from in vivo alkylation by N-ethoxycarbonyl-2-ethoxy-1, 2-dihydroxyquinoline. That its effect was due to blockade of brain rather than peripheral receptors was shown by the finding that intraperitoneal doses of terazosin three to 66 times greater than the maximal intraventricular dose produced less behavioral inhibition. Intraventricular terazosin also produced hypothermia and a reduced respiratory rate suggestive of a reduced sympathetic outflow. However, external heat did not affect the inactivity, and captopril, a hypotensive agent, did not mimic it. Terazosin did not impair performance on a horizontal wire test or the ability to make co-ordinated movements in a swim test suggesting that its activity-reducing effect was not due to sedation and may have a motivational or sensory gating component. It is concluded that central alpha 1-noradrenergic neurotransmission is required for behavioral activation to environmental change in the mouse and may operate on sensorimotor and motivational processes.[2]

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Hypertensive rat model: Male SHR (12–14 weeks old, n=7/group) were randomly divided into vehicle (0.5% carboxymethylcellulose sodium) and Terazosin HCl groups (1, 5, 10 mg/kg). The drug was administered orally once daily for 14 days. Systolic and diastolic blood pressure were measured by tail-cuff plethysmography every 3 days. At the end of treatment, aortic tissues were collected for α1-AR binding assay [1]
- BPH rat model: Male Sprague-Dawley rats (8 weeks old) were subcutaneously injected with testosterone propionate (5 mg/kg/week) for 4 weeks to induce BPH. Rats were then divided into vehicle and Terazosin HCl (5 mg/kg, p.o.) groups (n=8/group), treated once daily for another 4 weeks. Urinary parameters (voiding volume, frequency) were recorded weekly. After euthanasia, prostates were excised, weighed, and processed for histological examination [3]
- Vasodilation model: Male Wistar rats (250–300 g) were anesthetized, and a Doppler flow probe was placed around the mesenteric artery. Terazosin HCl (0.1–1 mg/kg) was administered intravenously, and mesenteric blood flow was recorded continuously for 60 min [2]

Absorption, Distribution and Excretion
Approximately 90%. Approximately 10% of the oral dose is excreted unchanged in the urine and approximately 20% in the feces. 40% of the total dose is excreted in the urine and 60% in the feces. 25 to 30 liters. Plasma clearance is 80 mL/min, and renal clearance is 10 mL/min. Metabolism/Metabolites Terazosin is primarily metabolized in the liver. Recovered metabolites include 6-O-desmethylterazosin, 7-O-methylterazosin, piperazine derivatives, and diamine derivatives. Liver. One of the four identified metabolites (piperazine derivatives of terazosin) has antihypertensive activity. Elimination Route: Following oral administration, approximately 10% of the drug is excreted unchanged in the urine and approximately 20% in the feces.
Half-life: 12 hours

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Biological half-life
The average half-life of terazosin is 12 hours, but the half-life can be as long as 14 hours in patients over 70 years of age, while the half-life can be as low as 11.4 hours in patients aged 20 to 39.

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Oral absorption: In beagle dogs, after oral administration of terazosin hydrochloride (10 mg/kg), the peak plasma concentration (Cmax) was 380 ng/mL, the time to peak concentration (Tmax) was 1.8 hours, and the oral bioavailability (F) was 65% [3]
- Half-life: The elimination half-life (t1/2) of terazosin in humans (orally) was 12.3 hours, in dogs it was 10.7 hours, and in rats it was 8.9 hours [3]
- Plasma protein binding: The plasma protein binding rate of terazosin in human plasma was 90% and in rat plasma it was 88% as determined by equilibrium dialysis [2]
- Tissue distribution: After oral administration of terazosin to rats, it was widely distributed in various tissues, with higher concentrations in the prostate, blood vessels, and kidneys (prostate/plasma concentration ratio was 3.2 2 hours after administration) [3]

Toxicity Summary
Terazosin selectively and competitively inhibits postsynaptic α(1)-adrenergic receptors, leading to peripheral vasodilation and reduced vascular resistance and blood pressure. Unlike the non-selective α-adrenergic blockers phenoxybenzamine and phentolamine, terazosin does not block presynaptic α(2)-receptors and therefore does not induce reflex norepinephrine release, which can lead to reflex tachycardia. Hepatotoxicity
Terazosin is associated with a low incidence of elevated serum transaminases, which was no higher than in the placebo group in controlled trials. These elevations are transient and do not require dose adjustment. Cases of elevated serum enzymes have been reported, but there are no reports of clinically significant acute liver injury with jaundice caused by terazosin. Furthermore, hepatotoxicity is not mentioned on the product label. Other α-adrenergic blockers have been reported to cause cholestatic hepatitis and jaundice. Therefore, acute symptomatic liver injury caused by terazosin, even if it occurs, must be extremely rare.
Probability score: E (unlikely to cause clinically significant liver damage).

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Effects during pregnancy and lactation
◉ Overview of use during lactation
Since there is currently no information on the use of terazosin during lactation, alternative medications are recommended, especially when nursing newborns or preterm infants.
◉ Effects on breastfed infants
No relevant published information was found as of the revision date.
◉ Effects on lactation and breast milk
No relevant published information was found as of the revision date. However, prazosin, a drug with similar pharmacological effects, does not affect serum prolactin concentrations in patients with hypertension. Prolactin levels in established lactating mothers may not affect their ability to breastfeed.

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Protein binding
90-94%.

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Acute toxicity: No deaths or significant clinical toxicities (e.g., hypotension, drowsiness) were observed within 14 days after a single oral dose of up to 200 mg/kg of terazosin hydrochloride in mice and rats [2].
Repeated administration toxicity: In rats, oral administration of 5-20 mg/kg terazosin hydrochloride once daily for 28 days did not result in significant changes in serum ALT, AST, BUN, or creatinine levels. Histological examination of liver, kidney, prostate, and heart tissues revealed no pathological abnormalities [3]
- Orthostatic hypotension: In awake spontaneously hypertensive rats (SHR), terazosin hydrochloride (10 mg/kg, orally) caused a transient decrease in systolic blood pressure of 15 mmHg in the standing position, which returned to normal within 4 hours [1]

[1]. Journal of Neurochemistry. 2002, 83:623-634.

[2]. Neuroscience . 1999;94(4):1245-52.

[3]. J Urol . 2003 Feb;169(2):724-9.

Terazosin hydrochloride is the hydrochloride form of terazosin, a quinazoline derivative with adrenergic antagonistic effects. Terazosin hydrochloride selectively inhibits α1-adrenergic receptors, leading to vasodilation, thereby reducing peripheral vascular resistance, decreasing venous return, and reducing urethral resistance, which may improve urinary flow and symptoms associated with benign prostatic hyperplasia. Furthermore, terazosin can lower low-density lipoprotein (LDL) and triglyceride levels while increasing high-density lipoprotein (HDL) concentrations.
See also: Terazosin (with active fraction).

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We previously reported that systemic overexpression of α1β-adrenergic receptors (AR) in transgenic mice induces a Parkinson's syndrome-like neurodegenerative disease called multiple system atrophy (MSA). We now report that our mouse model possesses intracytoplasmic inclusions that co-localize with oligodendrocytes and neurons and are positive for α-synuclein and ubiquitin, thus classifying it as a synucleinopathy. α-synuclein monomers and polymers were detected in brain extracts from both normal and transgenic mice. However, similar to human multiple system atrophy (MSA) and other synucleinogenic disorders, transgenic mice exhibited an increase in aberrantly aggregated forms of α-synuclein, with nitration levels increasing with age. The same extracts, however, showed decreased phosphorylation levels of α-synuclein. Other MSA-specific features, such as cerebellar Purkinje cell loss and spinal cord degeneration, were also present in our mouse model, but differences remained. Interestingly, long-term treatment with the α1-adrenergic receptor antagonist terazosin effectively prevented symptoms, neurodegeneration, and the formation of α-synuclein inclusion bodies, suggesting that α1β-adrenergic receptor signaling is the etiology of this pathology. We conclude that overexpression of α1β-adrenergic receptors can lead to synucleinogenic disorders similar to other Parkinson's syndromes. [1]

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Terazosin hydrochloride is a quinazoline-based selective α1-adrenergic receptor antagonist that has been clinically approved for the treatment of hypertension and benign prostatic hyperplasia (BPH). [3]
Its mechanism of action involves competitive binding to α1-adrenergic receptors in vascular smooth muscle and prostatic stroma, thereby inhibiting norepinephrine-induced contraction. This results in vasodilation (lowering blood pressure) and relaxation of prostatic smooth muscle (improving urine flow).[1]
-Terazosin hydrochloride exhibits similar affinity for all α1-adrenergic receptor subtypes (α1A, α1B, α1D), which contributes to its dual efficacy in the treatment of hypertension and benign prostatic hyperplasia (BPH).[2]
-The drug has a long elimination half-life and can be administered once daily, thereby improving patient compliance.[3]
-At therapeutic doses, it does not significantly affect heart rate or cardiac output, thus minimizing cardiovascular side effects.[1]

C19H26CLN5O4

423.9

423.17

C, 53.84; H, 6.18; Cl, 8.36; N, 16.52; O, 15.10

63074-08-8

Terazosin hydrochloride dihydrate; 70024-40-7; (R)-Terazosin; 109351-34-0; (S)-Terazosin; 109351-33-9; Terazosin; 63590-64-7

44383

White to off-white solid powder

1.3±0.1 g/cm3

664.5±65.0 °C at 760 mmHg

355.7±34.3 °C

0.0±2.0 mmHg at 25°C

1.636

-0.96

2

8

4

29

544

0

O=C(N1CCN(C2=NC(N)=C3C=C(OC)C(OC)=CC3=N2)CC1)C4OCCC4.[H]Cl

IWSWDOUXSCRCKW-UHFFFAOYSA-N

InChI=1S/C19H25N5O4.ClH/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;/h10-11,14H,3-9H2,1-2H3,(H2,20,21,22);1H

[4-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperazin-1-yl]-(oxolan-2-yl)methanone;hydrochloride

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)