Antipsychotic drugs: comparison in animal models of efficacy, neurotransmitter regulation, and neuroprotection.

Various lines of evidence indicate the presence of progressive pathophysiological processes occurring within the brains of patients with schizophrenia. By modulating chemical neurotransmission, antipsychotic drugs may influence a variety of functions regulating neuronal resilience and viability and have the potential for neuroprotection. This article reviews the current literature describing preclinical and clinical studies that evaluate the efficacy of antipsychotic drugs, their mechanism of action and the potential of first- and second-generation antipsychotic drugs to exert effects on cellular processes that may be neuroprotective in schizophrenia.

Role of nitric oxide and mitochondria in control of firefly flash.

In light-producing cells (photocytes) of the firefly light organ, mitochondria are clustered in the cell periphery, positioned between the tracheolar air supply and the oxygen-requiring bioluminescent reactants which are sequestered in more centrally-localized peroxisomes. This relative positioning suggests that mitochondria could control oxygen availability for the light reaction. We hypothesized that active cellular respiration would make the interior regions of the photocytes relatively hypoxic, and that the "on" signal for production of bioluminescence might depend on inhibition of mitochondrial oxygen consumption, which would allow delivered oxygen to pass through the peripheral mitochondrial zone to reach peroxisomes deep in the cell interior.

Differential effects of typical and atypical neuroleptics on mitochondrial function in vitro.

A series of typical (chlorpromazine, haloperidol and thioridazine) and atypical (risperidone, quetiapine, clozapine and olanzapine) antipsychotics were tested for effects on integrated bioenergetic functions of isolated rat liver mitochondria. Polarographic measurement of oxygen consumption in freshly isolated mitochondria showed that electron transfer activity at respiratory complex I is inhibited by chlorpromazine, haloperidol, risperidone, and quetiapine, but not by clozapine, olanzapine, or thioridazine. Chlorpromazine and thioridazine act as modest uncouplers of oxidative phosphorylation.

Permeability transition in rat liver mitochondria is modulated by the ATP-Mg/Pi carrier.

Mitochondrial permeability transition, due to opening of the permeability transition pore (PTP), is triggered by Ca2+ in conjunction with an inducing agent such as phosphate. However, incubation of rat liver mitochondria in the presence of low micromolar concentrations of Ca2+ and millimolar concentrations of phosphate is known to also cause net efflux of matrix adenine nucleotides via the ATP-Mg/Pi carrier. This raises the possibility that adenine nucleotide depletion through this mechanism contributes to mitochondrial permeability transition.