イソプレナリン

1.4

-0.61

151.0 Ų [M+H]+ [CCS Type: DT; Buffer gas: N2; Ionization: ESI+; Dataset: TOXCAST; Source Identifier: DTXSID6025486]

147.87 Ų [M+K]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

149.4 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

150 Ų [M+H]+ [CCS Type: DT; Method: single field calibrated]

Signs and Symptoms of Overdose

The pharmacologic effects of isoproterenol are at least in part attributable to stimulation through beta-adrenergic receptors of intracellular adenyl cyclase, the enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic AMP. Increased cyclic AMP levels are associated with relaxation of bronchial smooth muscle and inhibition of release of mediators of immediate hypersensitivity from cells, especially from mast cells.

Benchmark Dataset for the Liver Toxicity Knowledge Base (LTKB)

isoproterenol

Alupent®

Adrenergics

Not Applicable

no-DILI-concern

C01CA02

C - Cardiovascular system

R - Respiratory system

R - Respiratory system

QR - Respiratory system

QC - Cardiovascular system

Isoprenaline is a non-selective beta adrenergic receptor agonist used in a number of indications for the heart, as well as bronchospasm in anesthesia. Isoprenaline has a short duration of action as it is rapidly cleared, and a wide therapeutic index. Patients should be counselled regarding the risks of isoprenaline in the treatment of cardiogenic shock following myocardial infarction, paradoxical worsening of heart block, or precipitation of Adams-Stokes attacks.

Isoprenaline is a non-selective beta adrenergic receptor agonist. Agonism of beta-1 and beta-2 adrenergic receptors causes the alpha subunit of G-protein coupled receptors to exchange GMP for GTP, activating them, and allowing the alpha subunit to dissociate from the beta and gamma subunits. Dissociation of the alpha subunit activates adenylate cyclase, converting ATP to cyclic AMP. Cyclic AMP activates protein kinase A (PKA), which phosphorylates cardiac L-type calcium channels such as Ca_v1.2. These channels depolarize cells by inward active transport of calcium ions. Agonism of beta-1 adrenergic receptors lead to increased strength of contractility, conduction of nerve impulses, speed of relaxation, and rate in the heart. Agonism of beta-2 adrenergic receptors leads to glycogenolysis in the liver, glucagon release from the pancreas, and activation of the renin-angiotensin-aldosterone system. In the alveoli, agonism of beta-2 adrenergic receptors, activates similar pathways to the heart, however the end result is regulation of sodium channels, the cystic fibrosis transmembrane conductance regulator (CFTR), and sodium potassium ATPase. PKA phosphorylates scaffolding proteins and sodium channels, increasing the number of sodium channels on the apical side of alveolar cells and increasing active transport of sodium ions into cells. Agonism of beta-2 adrenergic receptors can also increase chloride ion transport across CFTR. Together, these actions lead to passive transport of water out of the alveoli, and the clearance of alveolar fluid.