<?xml version="1.0" encoding="UTF-8"?>
<compound>
  <id type="integer">3586</id>
  <title>T3D3544</title>
  <common-name>Verapamil</common-name>
  <description>Verapamil is only found in individuals that have used or taken this drug. Verapamil is a calcium channel blocker that is a class IV anti-arrhythmia agent. [PubChem]Verapamil inhibits voltage-dependent calcium channels. Specifically, its effect on L-type calcium channels in the heart causes a reduction in ionotropy and chronotropy, thuis reducing heart rate and blood pressure. Verapamil's mechanism of effect in cluster headache is thought to be linked to its calcium-channel blocker effect, but which channel subtypes are involved is presently not known. [PubChem] Calcium channel antagonists can be quite toxic. In the management of poisoning, early recognition is critical. Calcium channel antagonists are frequently prescribed, and the potential for serious morbidity and mortality with over dosage is significant. Ingestion of these agents should be suspected in any patient who presents in an overdose situation with unexplained hypotension and conduction abnormalities. The potential for toxicity should be noted in patients with underlying hepatic or renal dysfunction who are receiving therapeutic doses. (A7844).</description>
  <cas>52-53-9</cas>
  <pubchem-id>2520</pubchem-id>
  <chemical-formula>C27H38N2O4</chemical-formula>
  <weight>454.283160</weight>
  <appearance nil="true"/>
  <melting-point>&lt; 25°C</melting-point>
  <boiling-point>243-246°C at 1.00E-02 mm Hg</boiling-point>
  <density nil="true"/>
  <solubility>4.47 mg/L</solubility>
  <specific-gravity nil="true"/>
  <flash-point nil="true"/>
  <vapour-pressure nil="true"/>
  <route-of-exposure>Orally, 90‰ЫТ100% of Verapamil is absorbed. Intravenous.</route-of-exposure>
  <target nil="true"/>
  <mechanism-of-toxicity>Verapamil inhibits voltage-dependent calcium channels. Specifically, its effect on L-type calcium channels in the heart causes a reduction in ionotropy and chronotropy, thuis reducing heart rate and blood pressure. Verapamil's mechanism of effect in cluster headache is thought to be linked to its calcium-channel blocker effect, but which channel subtypes are involved is presently not known.</mechanism-of-toxicity>
  <metabolism>Route of Elimination: Approximately 70% of an administered dose is excreted as metabolites in the urine and 16% or more in the feces within 5 days. About 3% to 4% is excreted in the urine as unchanged drug.Half Life: 2.8-7.4 hours</metabolism>
  <toxicity>LD50: 8 mg/kg (Intravenous, Mouse) (A308)</toxicity>
  <lethaldose nil="true"/>
  <carcinogenicity>No indication of carcinogenicity to humans (not listed by IARC).</carcinogenicity>
  <use-source>Drug used for the treatment of hypertension, angina, and cluster headache prophylaxis.</use-source>
  <min-risk-level nil="true"/>
  <health-effects>Cardiovascular: angina pectoris, AV block (2&amp;#176; &amp; 3&amp;#176;), atrioventricular dissociation, CHF, pulmonary edema, chest pain, claudication, myocardial infarction, palpitations, purpura (vasculitis), syncope.Digestive system: diarrhea, dry mouth, gastrointestinal distress, gingival hyperplasia.Hemic and lymphatic: ecchymosis or bruising.Nervous system: cerebrovascular accident, confusion, equilibrium disorders, insomnia, muscle cramps, psychotic symptoms, shakiness, somnolence, extrapyramidal symptoms.Skin: arthralgia and rash, exanthema, hair loss, hyperkeratosis, macules, sweating, urticaria, Stevens-Johnson syndrome, erythema multiforme.Special senses: blurred vision, tinnitus.Urogenital: gynecomastia, galactorrhea/hyperprolactinemia, increased urination, spotty menstruation, impotence.</health-effects>
  <symptoms>The resultant inhibition of the contractile processes of the myocardial smooth muscle cells leads to dilation of the coronary and systemic arteries,improved oxygen delivery to the myocardial tissue, and decreased total peripheral resistance, systemic blood pressure, and afterload.
</symptoms>
  <treatment>Treatment of overdosage should be supportive. Beta-adrenergic stimulation or parenteral administration of calcium solutions may increase calcium ion flux across the slow channel and have been used effectively in treatment of deliberate overdosage with verapamil. In a few reported cases, overdose with calcium channel blockers has been associated with hypotension and bradycardia, initially refractory to atropine but becoming more responsive to this treatment when the patients received large doses (close to 1 gram/hour for more than 24 hours) of calcium chloride. Verapamil cannot be removed by hemodialysis. Clinically significant hypotensive reactions or high degree AV block should be treated with vasopressor agents or cardiac pacing, respectively. Asystole should be handled by the usual measures including cardiopulmonary resuscitation. (L1712)</treatment>
  <created-at type="dateTime">2009-07-30T17:59:14Z</created-at>
  <updated-at type="dateTime">2014-12-24T20:26:08Z</updated-at>
  <interacting-proteins nil="true"/>
  <wikipedia>Verapamil</wikipedia>
  <uniprot-id></uniprot-id>
  <kegg-compound-id>C07188</kegg-compound-id>
  <omim-id></omim-id>
  <chebi-id>9948</chebi-id>
  <biocyc-id></biocyc-id>
  <ctd-id nil="true"/>
  <stitch-id>Verapamil </stitch-id>
  <drugbank-id>DB00661</drugbank-id>
  <pdb-id></pdb-id>
  <actor-id nil="true"/>
  <organism nil="true"/>
  <export type="boolean">true</export>
  <metabolizing-proteins nil="true"/>
  <transporting-proteins nil="true"/>
  <moldb-smiles>COC1=C(OC)C=C(CCN(C)CCCC(C#N)(C(C)C)C2=CC(OC)=C(OC)C=C2)C=C1</moldb-smiles>
  <moldb-formula>C27H38N2O4</moldb-formula>
  <moldb-inchi>InChI=1/C27H38N2O4/c1-20(2)27(19-28,22-10-12-24(31-5)26(18-22)33-7)14-8-15-29(3)16-13-21-9-11-23(30-4)25(17-21)32-6/h9-12,17-18,20H,8,13-16H2,1-7H3</moldb-inchi>
  <moldb-inchikey>InChIKey=SGTNSNPWRIOYBX-UHFFFAOYNA-N</moldb-inchikey>
  <moldb-average-mass type="decimal">454.6016</moldb-average-mass>
  <moldb-mono-mass type="decimal">454.283157714</moldb-mono-mass>
  <origin>Exogenous</origin>
  <state>Liquid</state>
  <logp>3.79</logp>
  <hmdb-id>HMDB01850</hmdb-id>
  <chembl-id>CHEMBL197</chembl-id>
  <chemspider-id>2425</chemspider-id>
  <structure-image-file-name nil="true"/>
  <structure-image-content-type nil="true"/>
  <structure-image-file-size type="integer" nil="true"/>
  <structure-image-updated-at type="dateTime" nil="true"/>
  <biodb-id nil="true"/>
  <synthesis-reference>&lt;p&gt;Philippe Baudier, Arthur De Boeck, Jacques Fossion, &amp;#8220;Novel galenic forms of verapamil, their preparation and medicines containing said novel galenic forms.&amp;#8221; U.S. Patent US4859469, issued April, 1987.&lt;/p&gt;</synthesis-reference>
  <structure-image-caption nil="true"/>
</compound>
