For treatment of schizophrenia, GEODON capsules should be administered at an initial daily dose of 20 mg BID with food. Daily dosage may subsequently be adjusted on the basis of individual clinical status up to 80 mg BID. Systematic evaluation of ziprasidone has shown that its efficacy in schizophrenia is maintained for periods of up to 52 weeks at a dose of 20 to 80 mg BID. For treatment of bipolar mania, oral ziprasidone should be administered at an initial daily dose of 40 mg BID with food. The dose should then be increased to 60 mg or 80 mg BID on the second day of treatment and subsequently adjusted on the basis of toleration and efficacy within the range 40-80 mg BID. The recommended dose for intramuscular administration is 10 to 20 mg administered as required up to a maximum dose of 40 mg per day. Doses of 10 mg may be administered every two hours; doses of 20 mg may be administered every four hours up to a maximum of 40 mg/day.

Standard receptor-binding methods were used to label dopamine D2 receptors using [3H]spiperone. Briefly, rats were sacrificed by decapitation and the brains rapidly removed. The corpus striatum was dissected and homogenized in 20 vol at 50 mM Tris HCl (pH 7.2) buffer using a Brinkman Polytron homogenizer (setting 7 for 15 s). The homogenate was centrifuged for 10 min at 40000g. The pellet was resuspended in fresh ice-cold 50 mM Tris (pH 7.2) buffer with the Polytron homogenizer and recentrifuged. The final pellet was resuspended in 50 mM Tris HCl buffer (pH 7.2) containing 1 mM MgCl2 and 100 mM NaCl. Assays were initiated by the addition of tissue to tubes containing [3H]spiperone (0.2 nM) and drug or buffer in a final volume of 1 mL. Blocking agents (500 nM cinanserin and 1 mM prazosin) were present to prevent [3H]spiperone from labeling 5-HT2 and R1 noradrenergic receptors. Nonspecific binding was defined as the radioligand bound in the presence of 10 uM (+)-butaclamol. After a 15 min incubation at 37 °C, tissue samples were filtered onto Whatman GF/B glass fiber filters using a Brandel harvester and rinsed two times with 5 mL of ice-cold 50 mM Tris HCl (pH 7.4) buffer. Filters were soaked in 10 mL of Ready-Safe (Beckman Instruments), and the radioactivity was quantified using liquid scintillation counting. Ziprasidone binds to D2 receptors with pKi of 8.32 nM.