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.

Generic name Ziprasidone
Brand Names/Synonyms Geodon; Zeldox; Ziprasidone
Indication For the treatment of schizophrenia
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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
The most recent additions to the antipsychotic armamentarium, ziprasidone (Geodon) and aripiprazole (Abilify), differ from the previously available products in ... - Psychiatric Times,

Understanding and Managing Psychosis in Late Life  May 15, 2006
...prescribed antipsychotics. Studies of ziprasidone (Geodon) in this population have not yet been published. Aripiprazole (Abilify ... - Psychiatric Times,

Aripiprazole in the Treatment of Patients With Borderline ...  May 10, 2006
Text]. Anghelescu I, Wolf J: Successful switch to aripiprazole after induction of hyperprolactinemia by ziprasidone: a case report. ... - Am J Psychiatry (subscription)

Behavioral and Pharmacologic Treatment of Aggression in Children ...  May 10, 2006
Clozapine (Clozaril), quetiapine (Seroquel), olanzapine (Zyprexa) and ziprasidone (Geodon) have been evaluated in small or uncontrolled studies and case ... - Psychiatric Times,

Innovations: Geriatric Psychiatry: Diagnosis and Treatment of ...  May 10, 2006
Olanzapine has also been shown to effective and well tolerated at dosages of 5 to 10 mg per day (8). Data for quetiapine, ziprasidone, and aripiprazole are ... - Psychiatric Services (subscription)

Self-Mutilation of Fingers After Cervical Spinal Cord Injury  May 9, 2006
We recommended a trial of ziprasidone and individual psychotherapy. ... Ziprasidone was recommended in this case to make use of its dopamine-antagonism properties. ... - Psychosomatics (subscription)

Antipsychotic Drug Use Growing Fastest Among Children  May 2, 2006
...receiving the latest generation of antipsychotics - known as atypical antipsychotics, including risperidone, olanzapine, clozapine, ziprasidone and quetiapine ... - YubaNet,

Management of Acute Undifferentiated Agitation in the Emergency ...  Apr 26, 2006
We have read with interest the recent article 1 that compared the efficacy of droperidol, ziprasidone, and midazolam for sedation in the emergency department ... - AEM (subscription)

Schizophrenia gene function offers hope for drug R&D  Apr 23, 2006
The newer atypical antipsychotic medications (such as clozapine, risperidone, olanzapine, quetiapine, ziprasidone and aripiprazole) are usually preferred over ... - DrugResearcher.com,

Droperidol Use in the Emergency Department Is Not Safe  Apr 26, 2006
Biros M. Management of acute undifferentiated agitation in the emergency department: A randomized double-blind trial of droperidol, ziprasidone, and midazolam. ... - AEM (subscription)

Pfizer profits soar despite slipping revenues  Apr 20, 2006
But strong growth from newer products such as schizophrenia drug Geodon (ziprasidone), up 32% to $182 million, and Lyrica (pregabalin) for epilepsy and pain ... - Pharma Times (subscription),

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

  1. Ziprasidone should not be used with any drug that prolongs the QT interval .
  2. Given the primary CNS effects of ziprasidone, caution should be used when it is taken in combination with other centrally acting drugs.
  3. Because of its potential for inducing hypotension, ziprasidone may enhance the effects of certain antihypertensive agents.
  4. Ziprasidone may antagonize the effects of levodopa and dopamine agonists.

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
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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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