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Ziprasidone
drug data and news
Ziprasidone drug data, resources, and news articles (when available). Onconews.org provides news on cancer research. This section, which includes profiles on medicines that may or not be cancer-related is in beta form. If things run smoothly we will be releasing a new format late in the summer of 2006.
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| Generic name | Ziprasidone | ||
| Brand Names/Synonyms | Geodon; Zeldox; Ziprasidone | ||
| Indication | For the treatment of schizophrenia | ||
| Sponsored links | Description | Not Available | |
| Pharmacology | Ziprasidone is a psychotropic agent belonging to the chemical class of benzisoxazole derivatives and is indicated for the treatment of schizophrenia. Ziprasidone is a selective monoaminergic antagonist with high affinity for the serotonin Type 2 (5HT2), dopamine Type 2 (D2), 1 and 2 adrenergic, and H1 histaminergic receptors. Ziprasidone acts as an antagonist at other receptors, but with lower potency. Antagonism at receptors other than dopamine and 5HT2 with similar receptor affinities may explain some of the other therapeutic and side effects of Ziprasidone. Ziprasidone's antagonism of muscarinic M1-5 receptors may explain its anticholinergic effects. Ziprasidone's antagonism of histamine H1 receptors may explain the somnolence observed with this drug. Ziprasidone's antagonism of adrenergic a1 receptors may explain the orthostatic hypotension observed with this drug. Ziprasidone functions as an antagonist at the Dopamine D2 , 5HT-2A , and 5HT-1D receptors, and as an agonist at the 5HT-1A receptor. Ziprasidone also inhibits synaptic reuptake of serotonin and norepinephrine. | ||
| Mechanism Of Action | The mechanism of action of Ziprasidone, as with other drugs used to treat schizophrenia, is unknown. Ziprasidone exhibited high in vitro binding affinity for the dopamine D2 and D3, the serotonin 5HT2A, 5HT2C, 5HT1A, 5HT1D and alpha 1-adrenergic receptors, and moderate affinity for the histamine H1 receptor. However, it has been proposed that the drug's therapeutic activity in schizophrenia is mediated through a combination of dopamine Type 2 (D2) and serotonin Type 2 (5HT2) receptor antagonism. | ||
| Ziprasidone News (When available) |
Recent Developments in Antipsychotic Use in Adults Apr 20, 2006 Understanding and Managing Psychosis in Late Life May 15, 2006 Aripiprazole in the Treatment of Patients With Borderline ... May 10, 2006 Behavioral and Pharmacologic Treatment of Aggression in Children ... May 10, 2006 Innovations: Geriatric Psychiatry: Diagnosis and Treatment of ... May 10, 2006 Self-Mutilation of Fingers After Cervical Spinal Cord Injury May 9, 2006 Antipsychotic Drug Use Growing Fastest Among Children May 2, 2006 Management of Acute Undifferentiated Agitation in the Emergency ... Apr 26, 2006 Schizophrenia gene function offers hope for drug R&D Apr 23, 2006 Droperidol Use in the Emergency Department Is Not Safe Apr 26, 2006 Pfizer profits soar despite slipping revenues Apr 20, 2006 | ||
| Dosage Forms | Capsule; Injection; | ||
| Drug_Category | Antipsychotics; Dopamine Antagonists; Serotonin Antagonist; ATC:N05AE04 | ||
| Absorption | ~60% | ||
| Interactions |
-->Interactions for Ziprasidone: Drug-drug interactions can be pharmacodynamic (combined pharmacologic effects) or pharmacokinetic (alteration of plasma levels). The risks of using ziprasidone in combination with other drugs have been evaluated as described below. Based upon the pharmacodynamic and pharmacokinetic profile of ziprasidone, possible interactions could be anticipated: Pharmacodynamic Interactions
Pharmacokinetic Interactions The Effect of Other Drugs on Ziprasidone Carbamazepine Carbamazepine is an inducer of CYP3A4; administration of 200 mg BID for 21 days resulted in a decrease of approximately 35% in the AUC of ziprasidone. This effect may be greater when higher doses of carbamazepine are administered. Ketoconazole Ketoconazole, a potent inhibitor of CYP3A4, at a dose of 400 mg QD for 5 days, increased the AUC and C max of ziprasidone by about 35-40%. Other inhibitors of CYP3A4 would be expected to have similar effects. Cimetidine Cimetidine at a dose of 800 mg QD for 2 days did not affect ziprasidone pharmacokinetics. Antacid The coadministration of 30 mL of MAALOX with ziprasidone did not affect the pharmacokinetics of ziprasidone. In addition, population pharmacokinetic analysis of schizophrenic patients enrolled in controlled clinical trials has not revealed evidence of any clinically significant pharmacokinetic interactions with benztropine, propranolol, or lorazepam. Effect of Ziprasidone on Other Drugs In vitro studies revealed little potential for ziprasidone to interfere with the metabolism of drugs cleared primarily by CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4, and little potential for drug interactions with ziprasidone due to displacement. Lithium Ziprasidone at a dose of 40 mg BID administered concomitantly with lithium at a dose of 450 mg BID for 7 days did not affect the steady-state level or renal clearance of lithium. Oral Contraceptives Ziprasidone at a dose of 20 mg BID did not affect the pharmacokinetics of concomitantly administered oral contraceptives, ethinylestradiol (0.03 mg) and levonorgestrel (0.15 mg). Dextromethorphan Consistent with in vitro results, a study in normal healthy volunteers showed that ziprasidone did not alter the metabolism of dextromethorphan, a CYP2D6 model substrate, to its major metabolite, dextrorphan. There was no statistically significant change in the urinary dextromethorphan/dextrorphan ratio. | ||
| Toxicity | Not Available | ||
| Organisms Affected | Humans and other mammals | ||
| Chemical IUPAC Name | 6-chloro-5-[2-[4-(7-thia-8-azabicyclo[4.3.0]nona-1,3,5,8-tetraen-9-yl)piperazin-1-yl]ethyl]-1,3-dihydroindol-2-one | ||
| Chemical Formula | C21H21ClN4OS | ||
| Molecular Weight | 412.936 g/mol | ||
| Smiles String | C1CN(CCN1CCC2=C(C=C3C(=C2)CC(=O)N3)Cl)C4=NSC5=CC=CC=C54 | ||
| Melting Point | >300 °C | ||
| Water Solubility | Not Available | ||
| State | Solid | ||
| LogP/Hphobicity | 3.813 | ||
| Isoelectric Point | Not Available | ||
| Biotransformation | Hepatic | ||
| Half Life | 7 hours | ||
| Protein Binding [%] | 99% | ||
| RxList Link | RXlist | ||
| Sponsored links | |||
| Drug Reference |
http://www.drugs.com/cons/Ziprasidone.html http://www.rxlist.com/cgi/generic2/ziprasidone.htm | ||
| Drug Type | Approved Drug | ||
| Accession No | APRD00540 | ||
| CAS Registry Number | 146939-27-7 | ||
| KEGG Compound ID | C07568 | ||
| PubChem ID | SID:210748 | ||
| PharmGKB ID | PA451974 | ||
| SwissProt ID | Not Available | ||
| GenBank ID | Not Available | ||
| Drug ID Number [DIN] | Not Available |
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