Author(s): Nandra KS, Agius M
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Abstract Recently, the pharmacological division between typical and atypical antipsychotics has been called into question. New evidence, however, continues to emerge showing differences between these two classes of drugs. Hence typical and atypical antipsychotics are clearly different classes of drugs, as evidenced by their actions, mechanisms, effects and side effects. The most recently investigated field in which both classes of drugs have opposing effects is neuron survival and neurogenesis. Schizophrenia has been found to be a disease of progressive reductions in grey matter, and the more lost, the worse the outcome. Medication naive patients have lowered levels of neurotrophins e.g. NT-3, NGF BDNF. The antipsychotic drugs alter the levels of these neurotrophins. Haloperidol, of the typical antipsychotics, causes neuron apoptosis by a free radical induced mechanism, involving Bcl-XS, P53, cytochrome c translocation and caspase 3 activation. Haloperidol also lowers BDNF levels, reducing neuroprotection in the brain to enable haloperidol's toxic effects. Atypical drugs have opposing effects. They increase levels of BDNF, improve cell survival and enhance neurogenesis. Atypical drugs can also prevent or reverse the effects of haloperidol induced toxicity. The mechanism involves the inverse agonism of 5HT receptors, particularly those of the 2A subset, but the situation is considerably more complicated.
This article was published in Psychiatr Danub
and referenced in Journal of Bioanalysis & Biomedicine