Pharmacodynamics +<unk>  Site Ki (nM) Species Ref 5-HT1A 55–272 Human 5-HT1B 56–85 Rat 5-HT1D 4,070 Pig 5-HT2A 4,280 Human 5-HT2B 457–513 ()166–316 () Human 5-HT2C 61,700 () 5,010 ()736–2,457 HumanHumanRodent 5-HT3 >10,000 Human α1 α2 1,297–2,789 Rat β1 0.02–2.69 Human β2 0.01–0.61 Human β3 450 Mouse D1 >10,000 Human D2 >10,000 Human H1 >10,000 Human 3,700 Rat 5,000 () Rat 29,000 () Rat >10,000 Rat Values are Ki (nM), unless otherwise noted. The smaller the value, the more strongly the drug binds to the site.<unk>  is classified as a competitive non-cardioselective sympatholytic<unk>  blocker that crosses the blood–brain barrier. It is lipid soluble and also has sodium channel blocking effects.<unk>  is a non-selective β-adrenergic receptor antagonist, or<unk>  blocker; that is, it blocks the action of epinephrine (adrenaline) and norepinephrine (noradrenaline) at both β1- and β2-adrenergic receptors. It has little intrinsic sympathomimetic activity, but has strong membrane stabilizing activity (only at high blood concentrations, e.g. overdose).<unk>  is able to cross the blood–brain barrier and exert effects in the central nervous system in addition to its peripheral activity. In addition to blockade of adrenergic receptors,<unk>  has very weak inhibitory effects on the norepinephrine transporter and/or weakly stimulates norepinephrine release (i.e., the concentration of norepinephrine is increased in the synapse). Since<unk>  blocks β-adrenoceptors, the increase in synaptic norepinephrine only results in α-adrenoceptor activation, with the α1-adrenoceptor being particularly important for effects observed in animal models. Therefore, it can be looked upon as a weak indirect α1-adrenoceptor agonist in addition to potent β-adrenoceptor antagonist. In addition to its effects on the adrenergic system, there is evidence that indicates that<unk>  may act as a weak antagonist of certain serotonin receptors, namely the 5-HT1A, 5-HT1B, and 5-HT2B receptors. The latter may be involved in the effectiveness of<unk>  in the treatment of migraine at high doses. Both enantiomers of<unk>  have a local anesthetic (topical) effect, which is normally mediated by blockade of voltage-gated sodium channels. Studies have demonstrated<unk> 's ability to block cardiac, neuronal, and skeletal voltage-gated sodium channels, accounting for its known membrane stabilizing effect and antiarrhythmic and other central nervous system effects. Mechanism of action<unk>  is a non-selective<unk>  receptor antagonist. This means that it does not have<unk> eference to<unk> -1 or<unk> -2 receptors. It competes with sympathomimetic neurotransmitters for binding to receptors, which inhibits sympathetic stimulation of the heart. Blockage of neurotransmitter binding to<unk>  1 receptors on cardiac myocytes inhibits activation of adenylate cyclase, which in turn inhibits cAMP synthesis leading to reduced PKA<unk> otein Kinase A) activation. This results in less calcium influx to cardiac myocytes through voltage gated L-type calcium channels meaning there is a decreased sympathetic effect on cardiac cells, resulting in antihypertensive effects including reduced heart rate and lower arterial blood<unk> essure. Blockage of neurotransmitter binding to B2 receptors on smooth muscle cells will increase contraction, which will increase hypertension. Pharmacokinetics<unk>  is rapidly and completely absorbed, with peak<unk> asma levels achieved about 1–3 hours after ingestion. More than 90% of the drug is found bound to<unk> asma<unk> otein in the blood. Coadministration with food appears to enhance bioavailability. Despite complete absorption,<unk>  has a variable bioavailability due to extensive first-pass metabolism. Hepatic impairment therefore increases its bioavailability. The main metabolite 4-hydroxypropranolol, with a longer half-life (5.2–7.5 hours) than the parent compound (3–4 hours), is also pharmacologically active. Most of the metabolites are excreted in the urine.<unk>  is a highly lipophilic drug achieving high concentrations in the brain. The duration of action of a single oral dose is longer than the half-life and may be up to 12 hours, if the single dose is high enough (e.g., 80 mg). Effective<unk> asma concentrations are between 10 and 100 mg/l. Toxic levels are associated with<unk> asma concentrations above 2000 mg/l.
Propranolol
Bupranolol
Brotizolam
Acebutolol
Atenolol
Clonidine
Drospirenone
Stanozolol