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Description: Ziprasidone (marketed as Geodon, Zeldox) was the fifth atypical antipsychotic to gain FDA approval (February 2001). Ziprasidone is Food and Drug Administration (FDA) approved for the treatment of schizophrenia, and the intramuscular injection form of ziprasidone is approved for acute agitation in schizophrenic patients. Ziprasidone has also received approval for acute treatment of mania associated with bipolar disorder. [Wikipedia]
Drug Type: Small Molecule; Approved
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.
Indication: For the treatment of schizophrenia
Half Life: 7 hours
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HTR1D 100 100
ADRB1 100 100
HTR2A 99 99
HTR1A 99 99
DRD4 99 99
DRD3 99 99
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Monoamine GPCRs 100 100
Rhodopsin Like 97 97
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View All Author iconAuthors
  • Fabio Romeo
  • Lewis Warrington
  • Philip D Harvey
  • Antony Loebel
  • Leslie Citrome
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  • Pfizer
  • Massachusetts General Hospital
  • Creighton University
  • Yale University
  • University of Texas Southwestern Medical Center
View All Affiliations icon Organizations
  • Brescia University School of Medicine
  • Nathan S. Kline Institute for Psychiatric Research
  • Emory University School of Medicine
  • University Medical Centre Utrecht
  • Stanford University

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