α1-adrenoceptor
Terazosin targets the alpha-1 (α1) adrenergic receptors located on vascular smooth muscle and in the prostate. As a selective α1-receptor antagonist, it blocks the effects of endogenous catecholamines like norepinephrine. This inhibition prevents vasoconstriction, leading to the relaxation of smooth muscle in blood vessels and the bladder neck. The primary mechanism of action is the competitive inhibition of norepinephrine at the α1 receptor site. This results in decreased peripheral vascular resistance, lowering blood pressure, and improved urine flow in patients with BPH.

Terazosin does not distinguish between the numerous clonal α1-adrenergic receptor subtypes that are temporarily expressed in COS cells [1].

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In vitro, Terazosin is characterized by its high affinity and selectivity for the alpha-1 adrenergic receptor. Its activity is often studied using radioligand binding assays to determine its Ki or IC50 against these receptors. While specific values are not detailed in the provided search results, it is well-established as a potent α1 antagonist. Functional assays, such as measuring the inhibition of norepinephrine-induced contraction in isolated vascular tissues, confirm its antagonist activity.

For the treatment of ureteral stones, terazosin may be given to facilitate stone transit. It has been observed that terazosin is a safe and effective treatment for distal ureteral stones, particularly those that measure more than 5 mm [3].

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In vivo, Terazosin is effective in lowering blood pressure and is used to treat hypertension and benign prostatic hyperplasia. It is well-absorbed after oral administration. Its antihypertensive effect is achieved through the dilation of both arterial and venous blood vessels. In BPH, it relaxes smooth muscle in the prostate and bladder neck, improving urine flow and reducing symptoms. While specific pharmacokinetic parameters like half-life are not provided in the search results, its clinical use is well-documented.

In vitro receptor binding assays are performed using membrane preparations from cells or tissues that express alpha-1 adrenergic receptors. These membranes are incubated with a radiolabeled antagonist, such as [³H]prazosin, and varying concentrations of Terazosin. After incubation, the samples are filtered to separate bound from free radioligand, and the radioactivity is counted. The Ki value is determined from the competition binding curves using non-linear regression analysis.

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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For in vitro cell-based functional assays, cells expressing alpha-1 adrenergic receptors are used. Intracellular calcium levels are measured as an indicator of receptor activation. Cells are pre-incubated with various concentrations of Terazosin, and then stimulated with an agonist like phenylephrine. The inhibition of the calcium response by the compound is measured, and the IC50 is calculated. This assay confirms the compound's functional antagonism of the receptor.

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

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In vivo animal models for hypertension involve administering Terazosin to spontaneously hypertensive rats. The drug is typically given orally, and blood pressure is monitored via an indwelling catheter. The reduction in mean arterial pressure is recorded over time. For BPH models, the effect of the compound on prostate size or urethral pressure is assessed. Pharmacokinetic parameters, such as Cmax, Tmax, and half-life, are determined by collecting blood samples at various time points post-administration and analyzing the plasma concentration using HPLC.

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. Plasma clearance is 25 to 30 liters. The plasma clearance is 80 ml/min, and the 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. Hepatic. One of the four identified metabolites (piperazine derivatives of terazosin) has antihypertensive activity. Elimination pathway: Approximately 10% of the oral dose 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.

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 were not 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, is extremely rare.
Probability Score: E (Unlikely to be the cause of clinically significant liver damage).
Pregnancy and Lactation Effects
◉ Overview of Use During Lactation
Since there is currently no information on the use of terazosin during lactation, alternative medications are recommended, especially for breastfeeding 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
As of the revision date, no relevant published information was found on lactating mothers. However, prazosin, a drug with similar pharmacological effects, does not affect serum prolactin concentrations in hypertensive patients. Prolactin levels in established lactating mothers may not affect their ability to breastfeed.
Protein Binding
90-94%.
Toxicity Data
LD50: 259.3 mg/kg (intravenous injection, mice) (A308)

[1]. Drugs for treatment of benign prostatic hyperplasia: affinity comparison at cloned alpha 1-adrenoceptor subtypes and in human prostate. J Auton Pharmacol. 1996 Feb;16(1):21-8.

[2]. Pharmacological tolerance to alpha 1-adrenergic receptor antagonism mediated by terazosin in humans. J Clin Invest. 1992 Nov;90(5):1763-8.

[3]. Efficacy of combination terazosin and nifedipine therapy in postoperative treatment of distal ureteral stones after transurethral ureteroscopic lithotripsy. J Int Med Res. 2020 Apr;48(4):300060520904851.

Terazosin belongs to the quinazoline, piperazine, and furan class of compounds, and is also a primary amino compound. It possesses antitumor, antihypertensive, and alpha-adrenergic receptor antagonistic effects. Terazosin is a quinazoline derivative, belonging to the alpha-1 selective adrenergic blocker class, and is indicated for the treatment of benign prostatic hyperplasia (BPH) and hypertension. Terazosin blocks the action of adrenaline on alpha-1 adrenergic receptors, thereby leading to relaxation of blood vessels and prostate smooth muscle. Terazosin is an alpha-adrenergic blocker. The mechanism of action of terazosin is as an alpha-adrenergic receptor antagonist. Terazosin is a non-selective alpha-1 adrenergic receptor antagonist used to treat hypertension and BPH. Terazosin treatment is associated with a low incidence of transient elevations in serum transaminases and rare cases of clinically significant acute liver injury. Terazosin is a selective alpha-1 receptor antagonist used to treat the symptoms of benign prostatic hyperplasia (BPH). It also has a blood pressure-lowering effect, making it the first-line drug for men with hypertension and benign prostatic hyperplasia (BPH). Its mechanism of action is to block the effects of adrenaline on bladder smooth muscle and blood vessel walls.
See also: Terazosin hydrochloride (salt form).
Drug Indications
Tetrazosin is indicated for the treatment of symptomatic benign prostatic hyperplasia and hypertension.
FDA Label
Mechanism of Action
Tetrazosin is selective for α1-adrenergic receptors, but not for all their subtypes. Inhibition of these α1-adrenergic receptors relaxes blood vessels and prostate smooth muscle, thereby lowering blood pressure and improving urine flow. Smooth muscle cells make up about 40% of the prostate volume, so their relaxation reduces urethral pressure. Studies have also shown that catecholamines can induce mitogenic factors, and α1-adrenergic receptor blockers inhibit this effect. The ultimate long-term mechanism of action of terazosin and other α1-adrenergic receptor blockers is the induction of prostate cell apoptosis. Terazosin treatment can enhance the expression of transforming growth factor β1 (TGF-β1), thereby upregulating the p27kip1 and caspase cascade.
Pharmacodynamics
Terazosin is a quinazoline derivative, belonging to the class of α1-selective adrenergic blockers.

C19H25N5O4ELEMENTALANALYSIS

387.43

387.191

63590-64-7

Terazosin hydrochloride dihydrate;70024-40-7;(R)-Terazosin;109351-34-0;(S)-Terazosin;109351-33-9;Terazosin hydrochloride;63074-08-8;Terazosin-d8;1006718-20-2

5401

White to off-white solid

1.332 g/cm3

664.5ºC at 760 mmHg

281-283°C

355.7ºC

1.64

1

8

4

28

544

0

O=C(N1CCN(C2=NC(N)=C3C=C(OC)C(OC)=CC3=N2)CC1)C4OCCC4

VCKUSRYTPJJLNI-UHFFFAOYSA-N

InChI=1S/C19H25N5O4/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)

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

Vasocard; terazosin; 63590-64-7; Terazosine; Fosfomic; Blavin; Flumarc; Vasomet; Terazosina; Hytrin

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

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

DMSO: ~20 mg/mL (~51.6 mM; with ultrasonication and warming by heating to 60°C)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.45 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), Clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (25.0 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (6.45 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), Clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (25.0 mg/mL) to 900 μL of 20% SBE-β-CD saline and mix well.
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.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (6.45 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), Clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (25.0 mg/mL) to 900 μL of corn oil and mix well.

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