10476-53-6

Usage

Uses

Used in Pharmaceutical Industry:
(+/-)-4-HYDROXYPROPRANOLOL, HYDROCHLORIDE is used as an active pharmaceutical ingredient for the treatment of various cardiovascular conditions. Its application is primarily due to its antihypertensive properties, which help in lowering blood pressure, as well as its antianginal effects, which can alleviate chest pain caused by insufficient blood supply to the heart.
Additionally, it is used as an antiarrhythmic agent (class II) for the management of abnormal heart rhythms, contributing to the stabilization of the heart's electrical activity and overall cardiovascular health.
Used in Research and Development:
In the field of research and development, (+/-)-4-HYDROXYPROPRANOLOL, HYDROCHLORIDE serves as a valuable compound for studying the effects of β-adrenergic blockers on the cardiovascular system. Its chemical properties and metabolite status make it an important tool for understanding the mechanisms of action and potential therapeutic applications of Propranolol and other related drugs.
Used in Drug Metabolism Studies:
(+/-)-4-HYDROXYPROPRANOLOL, HYDROCHLORIDE is also utilized in drug metabolism studies to investigate the metabolic pathways and pharmacokinetics of Propranolol. This helps in optimizing drug dosages, understanding drug interactions, and identifying potential side effects or toxicities associated with the parent compound.

InChI:InChI=1/C16H21NO3/c1-2-9-17-10-12(18)11-20-16-8-7-15(19)13-5-3-4-6-14(13)16/h3-8,12,17-19H,2,9-11H2,1H3

Upstream product

• 18507-09-0 4-Methoxypropranolol 
• 318-98-9 Inderal 
• 525-66-6 propranolol 
• 84-85-5 4-methoxynaphth-1-ol 
• 90-15-3 α-naphthol 
• 2461-42-9 3-(1-naphthyloxy)-1,2-epoxypropane 
• 14133-79-0 (+/-)-4-Methoxypropranolol hydrochloride 

Downstream Products

• 130-15-4 [1,4]naphthoquinone 

Relevant academic research and scientific papers

Covalent binding of a reactive metabolite derived from propranolol and its active metabolite 4-hydroxypropranolol to hepatic microsomal proteins of the rat

Repeated administration of propranolol (PL) to rats causes the inhibition of cytochrome P450-2D (P450-2D) enzyme. We recently found that 4- hydroxypropranolol (4-OH-PL) was biotransformed to 1,4-naphthoquinone (1,4- NQ) by superoxide (SO) anions in medium containing rat liver microsomes and NADPH and proposed that the binding of the quinone to P450-2D apoproteins might be one of mechanisms for the enzyme inhibition [Narimatsu et al. (1995) Chem. Res. Toxicol. 8, 721-728]. In this study, we have searched for possible sources of SO for the conversion of 4-OH-PL to 1,4-NQ in rat liver microsomes and determined the radioactivity covalently bound to microsomal proteins after incubation of radioactive PL and 4-OH-PL with rat liver microsomes. Elimination of 4-OH-PL from a mixture containing microsomes and NADPH was suppressed by carbon monoxide. Antibodies raised to P450-2B1 and -3A2 partially, and antibody against NADPH-cytochrome P450 reductase (fp2) markedly suppressed the reaction. 1,4-NQ was formed concomitantly with 4-OH- PL elimination by a reconstituted preparation of fp2. Binding studies using naphthalene ring (NR)- and side chain (SC)-radiolabeled PL and 4-OH-PL showed that radioactivity covalently bound to microsomal proteins was much higher from 4-OH-PL than from PL for the NR-labeled compounds, but higher from PL than from 4-OH-PL for the SC-labeled compounds. These results suggest that the 4-OH-PL formed from PL by P450-2D enzyme is converted to 1,4-NQ with loss of the side chain, and the 1,4-NQ accounts for most of the radioactivity covalently bound to microsomal proteins, including the P450-2D enzymes. The SO for conversion of 4-OH-PL to 1,4-NQ is supplied mainly by fp2 with some contribution by P450 enzymes.

A new standardized electrochemical array for drug metabolic profiling with human cytochromes P450

Over the past two decades, a wealth of information on the human cytochrome P450 enzymes and their role in drug metabolism both in vitro and in vivo has been gathered. Our understanding of this area has progressed greatly, but our confidence in the develop

Multistage Reactive Transmission-Mode Desorption Electrospray Ionization Mass Spectrometry

Elucidating reaction mechanisms is important for advancing many areas of science such as catalyst development. It is often difficult to probe fast reactions at ambient conditions with high temporal resolution. In addition, systems involving reagents that

Product inhibition and dose-dependent bioavailability of propranolol in the isolated perfused rat liver preparation

We investigated in the isolated perfused rat liver (IPRL) whether product inhibition of metabolism contributes to the dose-dependent bioavailability of propranolol, a drug with a high, but saturable, hepatic first-pass effect. (±)-Propranolol was infused in the IPRL, using a recirculating design, for three 36-min periods (n = 9). Mean steady-state reservoir, i.e. hepatic inflow concentrations (C(in)), were 4.97, 10.4, and 20.4 μM, respectively. Mean reservoir concentrations of the metabolites 4'-hydroxypropranolol, 5'- hydroxypropranolol, N-desisopropylpropranolol, and naphthoxylactic acid (NLA), a major side-chain-oxidation metabolite, increased disproportionately with propranolol dose, but their production rate did not reach steady state. In separate experiments (n = 4), perfusate containing 7.1, 12.8, and 21.6 μM (±)-propranolol, corresponding to administration rates of 114, 205, and 346 nmol/min, respectively, was passed through the liver for 30 min each using a single-pass design. The bioavailability (hepatic outflow concentration/C(in)) of propranolol increased with C(in) from 0.012 to 0.150 to 0.288 in the recirculating IPRL. In the single-pass IPRL the increase (0.0077 in 0.0669 to 0.136) was significantly less (P 0.001). The greater bioavailability of propranolol in recirculating experiments was attributed to product inhibition since metabolites do not accumulate with the single-pass design. NLA did not appear to be the inhibiting metabolite because in further single-pass experiments with propranolol C(in) of 21.6 μM the presence of NLA (21.6 μM) in perfusate had no effect on propranolol bioavailability (n = 7) compared with control experiments (n = 5). These data suggest that, with the recirculating IPRL, dose-dependent bioavailability of propranolol is due to competitive inhibition of propranolol metabolism by propranolol metabolites, which is distinct from the noncompetitive product inhibition that has been reported to accompany chronic propranolol administration.