5-HT_1A Receptor

Alprenolol (p.o., 50 mg/kg) results in a significant reduction in blood pressure, averaging 20 mm Hg, and an increase in heart rate, averaging 39 beats/min (at 3-hr) in conscious renal hypertensive dogs[1].
Alprenolol (i.p., 5 mg/kg) efficiently inhibits the anxiolytic effects of indorenate and ipsapirone while having no effect on motor activity the anxiolytic effects of indorenate and ipsapirone but do not reduce the motor activity in adult male Swiss Webster mice[2].
Alprenolol (intravenous injection, 0.5 or 1.0 mg/kg) can reduce heart rate by 23 beats per minute, diastolic pressure by 10 mm Hg, and systolic pressure by 10 mm Hg. It can also slightly reduce liver and myocardial blood flows by 15% and 17%, respectively at a dose of 1.0 mg/kg in cats[3].

Aprapralol (oral, 50 mg/kg) significantly reduced blood pressure by an average of 20 mm Hg (3 hours) and increased heart rate by 39 beats/minute (3 hours) in conscious renally hypertensive dogs. 1]. Aprellol (intraperitoneal injection, 5 mg/kg) effectively blocks the anxiolytic effects of indomethacin and ixabepilone, but does not reduce locomotor activity in adult male Swiss Webster mice [2]. Aprapralol (intravenous injection, 0.5 or 1.0 mg/kg) can reduce systolic blood pressure by an average of 10 mm Hg and diastolic blood pressure by an average of 10 mm Hg), reduce heart rate by 23 beats/min, and slightly reduce myocardial contractility. At a dose of 1.0 mg/kg, liver blood flow in cats decreased by an average of 17% and 15% respectively [3].

The effects of pindolol, 10 mg/kg, alprenolol, 50 mg/kg, and practolol, 50 mg/kg, given by mouth, on blood pressure and heart rate were investigated over a 24-hr period in 5 conscious renal hypertensive dogs, using a cross-over design. Pindolol and alprenolol caused significant falls in blood pressure which averaged 22 mm Hg (at 3-hr after p.o. administration) and 20 mm Hg (at 3-hr). However, practolol failed to produce any significant changes in blood pressure. Heart rate increased by 67 beats/min (at 1-hr) and 39 beats/min (at 3-hr) after pindolol and alprenolol, respectively, but did not show any significant increase when practolol was given orally. The pindolol-induced tachycardia and hypotension were not suppressed significantly by propranolol (1 mg/kg i.v.) which blocked completely the tachycardia and hypotension induced by isoprenaline (3 mg/kg p.o.). The hypotension and tachycardia observed after oral administration of D-32 (50 mg/kg) or after intravenous infusion of p-OH D-32 (1 mg/kg per min for 5 min) were also not modified significantly by propranolol (1 mg/kg i.v.). Based on these results and other published data, mechanisms pertaining to the hypotension exerted by beta-adrenoceptor blocking agents were discussed. [1]

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The systemic injection of diazepam (0.5 and 1.0 mg/kg), indorenate (5 and 10 mg/kg) and ipsapirone (2.5 and 5.0 mg/kg) reduced anxiety as tested in an exploratory avoidance model in mice. The injection of pindolol (2.0 mg/kg), alprenolol (5.0 mg/kg) or methiotepin (0.25 mg/kg) effectively prevented the anxiolytic action of indorenate and ipsapirone. The combined treatment of the antagonists with indorenate or ipsapirone did not reduce the motor activity, therefore suggesting that the inhibition of exploratory behaviour, after such combinations, was not mediated through a general motor impairment. Neither diazepam nor indorenate alone modified the motor activity; ipsapirone (5 and 2.5 mg/kg), however, reduced ambulation. This reduction was also prevented by administering pindolol, alprenolol or methiotepin. These observations suggest that the anxiolytic actions of indorenate and ipsapirone are mediated via stimulation of the 5-HT1A like receptor subtype. [2]

Metabolism / Metabolites
Hepatic. One of the active metabolites, 4-OH-alprenolol, is an active beta-blocker.

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Biological Half-Life
2-3 hours

Protein Binding
80-90%

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women LDLo oral 210 mg/kg Ugeskrift for Laeger. Doctor's Weekly., 139(2817), 1977 [PMID:595169]
mouse LD50 intraperitoneal 90 mg/kg European Journal of Medicinal Chemistry--Chimie Therapeutique., 18(151), 1983
mouse LD50 intravenous 20 mg/kg AUTONOMIC NERVOUS SYSTEM: SYMPATHOMIMETIC Arzneimittel-Forschung. Drug Research., 27(1022), 1977 [PMID:18157]
mammal (species unspecified) LD50 oral 184 mg/kg Pharmaceutical Chemistry Journal, 8(137), 1974
mammal (species unspecified) LD50 intraperitoneal 102 mg/kg Pharmaceutical Chemistry Journal, 8(137), 1974

[1]. Effects of beta-adrenoceptor blocking agents, pindolol, alprenolol and practolol on blood pressure and heart rate in conscious renal hypertensive dogs. Arch Int Pharmacodyn Ther. 1977 Jan;225(1):152-65.

[2]. Evidence for the involvement of the 5-HT1A receptor in the anxiolytic action of indorenate and ipsapirone. Psychopharmacology (Berl). 1990;101(3):354-8.

[3]. Myocardial and haemodynamic effects of the beta-adrenoceptor blocking drug alprenolol (H56/28) in anaesthetized cats. Br J Pharmacol. 1969 Oct;37(2):357-66.

Alprenolol is a secondary alcohol that is propan-2-ol substituted by a 2-allylphenoxy group at position 1 and an isopropylamino group at position 3. It is a beta-adrenergic antagonist used as a antihypertensive, anti-arrhythmia and a sympatholytic agent. It has a role as an anti-arrhythmia drug, an antihypertensive agent, a beta-adrenergic antagonist and a sympatholytic agent. It is a secondary alcohol and a secondary amino compound.
One of the adrenergic beta-antagonists used as an antihypertensive, anti-anginal, and anti-arrhythmic agent. Alprenolol is no longer marketed by AstraZeneca, but may still be available in generic varieties.
One of the ADRENERGIC BETA-ANTAGONISTS used as an antihypertensive, anti-anginal, and anti-arrhythmic agent.

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Drug Indication
For the treatment of hypertension, angina, and arrhythmia

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Mechanism of Action
Alprenolol non-selectively blocks beta-1 adrenergic receptors mainly in the heart, inhibiting the effects of epinephrine and norepinephrine resulting in a decrease in heart rate and blood pressure. Also, with a more minor effect, by binding beta-2 receptors in the juxtaglomerular apparatus, alprenolol inhibits the production of renin, thereby inhibiting angiotensin II and aldosterone production and therefore inhibits the vasoconstriction and water retention due to angiotensin II and aldosterone, respectively.

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Pharmacodynamics
Alprenolol is a non-selective beta-blocker used in the treatment of hypertension, edema, ventricular tachycardias, and atrial fibrillation. Alprenolol impairs AV node conduction and decreases sinus rate and may also increase plasma triglycerides and decrease HDL-cholesterol levels. Alprenolol is nonpolar and hydrophobic, with low to moderate lipid solubility. Alprenolol has little to no intrinsic sympathomimetic activity and, unlike some other beta-adrenergic blocking agents, alprenolol has little direct myocardial depressant activity and does not have an anesthetic-like membrane-stabilizing action.

C₁₅H₂₃NO₂

249.35

249.173

C, 72.25; H, 9.30; N, 5.62; O, 12.83

13655-52-2

67824-72-0 (benzoate); 15020-61-8; 13707-88-5 (HCl); 15020-61-8; 15020-61-8 (HCl R-isomer); 13707-88-5; 15132-12-4 (HCl S-isomer); 16768-36-8; 21378-88-1 (tartrate); 23846-72-2; 100897-05-0 (tartrate R-isomer); 23846-71-1; 16768-36-8 (tartrate S-isomer); 13655-52-2; 23846-72-2

2119

White to off-white solid powder

1.007g/cm3

383.4ºC at 760mmHg

57.5°C

185.7ºC

1.46E-06mmHg at 25°C

1.5250 (estimate)

2.543

2

3

8

18

231

0

PAZJSJFMUHDSTF-UHFFFAOYSA-N

InChI=1S/C15H23NO2/c1-4-7-13-8-5-6-9-15(13)18-11-14(17)10-16-12(2)3/h4-6,8-9,12,14,16-17H,1,7,10-11H2,2-3H3

1-(propan-2-ylamino)-3-(2-prop-2-enylphenoxy)propan-2-ol

(RS)-Alprenolol; dl-Alprenolol; alprenolol; 13655-52-2; Alpheprol; Alfeprol; Alprenololum; Alfeprol [Russian]; Alprenololum [INN-Latin]; Alprenolol [INN:BAN]; Alprenolol

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product is not stable in solution, please use freshly prepared working solution for optimal results.

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

DMSO: ~100 mg/mL (~401.4 mM)
H2O: ~0.7 mg/mL (~2.7 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (10.03 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 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 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to 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 (10.03 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 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
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 (10.03 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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 4 mg/mL (16.04 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication (<60°C).

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