🧬 Receptor activity
| Target | Action | Affinity | Source | |
|---|---|---|---|---|
| Beta-2 adrenergic receptor | — | Ki 2.27 nM | CHEMBL | TargetBeta-2 adrenergic receptor Action— AffinityKi 2.27 nM SourceCHEMBL |
| Sigma non-opioid intracellular receptor 1 | — | Ki 95.38 nM | CHEMBL | TargetSigma non-opioid intracellular receptor 1 Action— AffinityKi 95.38 nM SourceCHEMBL |
| Sigma intracellular receptor 2 | — | Ki 352.9 nM | CHEMBL | TargetSigma intracellular receptor 2 Action— AffinityKi 352.9 nM SourceCHEMBL |
| 5-hydroxytryptamine receptor 6 | — | Ki 542 nM | CHEMBL | Target5-hydroxytryptamine receptor 6 Action— AffinityKi 542 nM SourceCHEMBL |
| 5-hydroxytryptamine receptor 1A | — | Ki 644.31 nM | CHEMBL | Target5-hydroxytryptamine receptor 1A Action— AffinityKi 644.31 nM SourceCHEMBL |
| 5-hydroxytryptamine receptor 2C | — | Ki 1373.1 nM | CHEMBL | Target5-hydroxytryptamine receptor 2C Action— AffinityKi 1373.1 nM SourceCHEMBL |
| 5-hydroxytryptamine receptor 2A | — | Ki 1790.2 nM | CHEMBL | Target5-hydroxytryptamine receptor 2A Action— AffinityKi 1790.2 nM SourceCHEMBL |
| Alpha-1B adrenergic receptor | — | Ki 10000 nM | CHEMBL | TargetAlpha-1B adrenergic receptor Action— AffinityKi 10000 nM SourceCHEMBL |
Mechanism of action
Propranolol is a nonselective β-adrenergic receptor antagonist. Blocking of these receptors leads to vasoconstriction, inhibition of angiogenic factors like vascular endothelial growth factor (VEGF) and basic growth factor of fibroblasts (bFGF), induction of apoptosis of endothelial cells, as well as down regulation of the renin-angiotensin-aldosterone system.
Pharmacodynamics
Propranolol is a beta-adrenergic receptor antagonist used to treat hypertension. Propranolol has a long duration of action as it is given once or twice daily depending on the indication. When patients abruptly stop taking propranolol, they may experience exacerbations of angina and myocardial infarctions.
Pharmacokinetics
Half-life
The elimination half-life of propranolol is approximately 8 hours. The plasma half-life of propranolol is 3 to 6 hours.
Absorption
Patients taking doses of 40mg, 80mg, 160mg, and 320mg daily experienced Cmax values of 18±15ng/mL, 52±51ng/mL, 121±98ng/mL, and 245±110ng/mL respectively. Propranolol has a Tmax of approximately 2 hours, though this can range from 1 to 4 hours in fasting patients. Taking propranolol with food does not increase Tmax but does increase bioavailability.
91% of an oral dose of propranolol is recovered as 12 metabolites in the urine.
The volume of distribution of propranolol is approximately 4L/kg or 320L.
The clearance of propranolol is 2.7±0.03L/h/kg in infants <90 days and 3.3±0.35L/h/kg in infants >90 days. Propranolol clearance increases linearly with hepatic blood flow. Propranolol has a clearance in hypertensive adults of 810mL/min.
Metabolism
Propranolol undergoes side chain oxidation to α-naphthoxylactic acid, ring oxidation to 4’-hydroxypropranolol, or glucuronidation to propranolol glucuronide. It can also be N-desisopropylated to become N-desisopropyl propranolol. 17% of a dose undergoes glucuronidation and 42% undergoes ring oxidation.
Propranolol has known human metabolites that include (2S,3S,4S,5R)-3,4,5-Trihydroxy-6-[1-naphthalen-1-yloxy-3-(propan-2-ylamino)propan-2-yl]oxyoxane-2-carboxylic acid.
Protein binding
Approximately 90% of propranolol is protein bound in plasma. Other studies have reported ranges of 85-96%.
External links
Fact-sheets from PsychonautWiki. Harm-reduction reference only — not medical advice.