α1-adrenoceptor

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

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].

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.

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.

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

---

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

Typically exists as solid at room temperature

1.332 g/cm3

664.5ºC at 760 mmHg

281-283°C

355.7ºC

1.64

1

8

4

28

544

0

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)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

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.

---

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).

View More

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)

---

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).

View More

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

---

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.

---

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