Ziprasidone: comprehensive overview and clinical use of a novel antipsychotic.

Ziprasidone (5-[2-(4-(1,2,-benzisothiazol-3-yl) piperazin-l-yl] ethyl]-6 -chloro indolin-2-one hydrochloride hydrate) is a novel antipsychotic with a pattern of receptor occupancy and preclinical attributes predictive of broad therapeutic efficacy and a favourable tolerability profile in the treatment of psychotic illness. Clinical trials indicate that ziprasidone is effective against positive, negative and affective symptoms in schizophrenia and schizoaffective disorder with minimal motor, cognitive, weight gain, prolactin related, or anticholinergic side effects. In addition, an im. formulation appears to be rapidly effective with significantly less motor side effect liability than haloperidol.

Substituted 2-benzothiazolamines as sodium flux inhibitors: quantitative structure-activity relationships and anticonvulsant activity.

Thirty-two aryl-substituted 2-benzothiazolamines have been tested for their ability to modulate sodium flux in rat cortical slices. A QSAR analysis, applied to these derivatives, showed a trend toward increasing potency as sodium flux inhibitors with increasing lipophilicity, decreasing size, and increasing electron withdrawal of the benzo ring substituents. Additionally, 4- or 5-substitution of the benzo ring was found to decrease potency. The combination of increased lipophilicity, small size, and electron withdrawal severely limited which groups were tolerated on the benzo ring, thus suggesting that the optimal substitution patterns have been prepared within this series. Nine of these compounds were potent inhibitors of veratridine-induced sodium flux (NaFl). These nine compounds also proved to be anticonvulsant in the maximal electroshock (MES) assay. Fourteen additional 2-benzothiazolamines demonstrated activity in the MES screen, yet exhibited no activity in the NaFl assay. These derivatives may be interacting at the sodium channel in a manner not discernible by the flux paradigm, or they may be acting by an alternative mechanism in vivo.

Dynamics of Imbibition in Phaseolus vulgaris L. in Relation to Initial Seed Moisture Content.

The seed moisture level marking the onset of imbibitional injury (breakpoint) was determined for two cultivars of Phaseolus vulgaris L. cvs ;Tendercrop' (TC) and ;Kinghorn Wax' (KW). At 20 degrees C the breakpoints were 0.15 gram H(2)O/gram dry weight (gram per gram) for TC and 0.11 gram per gram for KW. When seeds were imbibed at 5 degrees C, the breakpoints were 0.19 gram per gram (TC) and 0.16 gram per gram (KW). Below the breakpoint germination changed 4.6%/0.01 gram per gram for all treatments. Imbibition rates were maximal at 0.07 gram per gram and 0.33 gram per gram after 20 minutes imbibition. Rates of electrolyte leakage were correlated with the imbibition rate maximum at 0.07 gram per gram but were unaffected by the maximum at 0.33 gram per gram. The transition from tightly bound to semibound water occurred at 0.09 gram per gram and 0.11 gram per gram for KW and TC, respectively. T1 values increased exponentially as seed moisture decreased from 0.47 gram per gram to 0.05 gram per gram. (13)C-NMR sugar signals increased at moisture levels above 0.14 gram per gram and plateaued at approximately 0.33 gram per gram seed moisture. These results suggest that the breakpoint moisture level for imbibitional damage is a function of temperature while the injury process is similar at both 5 and 20 degrees C. Imbibition and leakage rate maxima reflect transitions in the states of seed water. NMR data support the application of the Water Replacement Hypothesis to seeds. Thus, imbibitional injury may be related to specific, temperature dependent moisture levels that are determined by water binding characteristics in the seed tissue.