Antipsychotics efficacy

In-Won C, Moore NA, Won-Keun O, et al. Behavioral pharmacology of polygalas-aponins indicates potential antipsychotic efficacy. Pharmacol Biochem Behav 2002 71 191-195. 

Neuroleptic activity profiles. The marked differences in action spectra of the phenothiazines, their derivatives and analogues, which may partially resemble those of butyrophenones, are important in determining therapeutic uses of neuroleptics. Relevant parameters include antipsychotic efficacy (symbolized by the arrow) the extent of sedation and the ability to induce ex-trapyramidal adverse effects. The latter depends on relative differences in antagonism towards dopamine and acetylcholine, respectively (p. 188). Thus, the butyrophenones carry an increased risk of adverse motor reactions because Lullmann, Color Atlas of Pharmacology 2000 Thieme All rights reserved. Usage subject to terms and oonditlons of lloense. 

Strong antipsychotic efficacy also in patients refractory to conventional neuroleptics... 

Each may have antipsychotic efficacy below EPS thresholds for many patients. 

Borison RL, Arvanitis LA, Miller BG, et al. ICI 204.636, an atypical antipsychotic efficacy and safety in a multicenter, placebo-controlled trial in patients with schizophrenia. J Clin Psychopharmacol 1996 16 158-169. 

In contrast to the difficult search for receptors responsible for antipsychotic efficacy, the differences in receptor effects of various antipsychotics do explain many of their toxicities (Tables 29-1 and 29-2). In particular, extrapyramidal toxicity appears to be consistently associated with high D2 potency. 

By the late 1960s and 1970s it was widely recognized that the key pharmacologic property of all neuroleptics with antipsychotic properties was their ability to block dopamine 2 receptors (Fig. 11-1). This action has proved to be responsible not only for the antipsychotic efficacy of conventional antipsychotic drugs but also for most of their undesirable side effects, including neurolepsis. 

FIGURE 11 — 2. The dopamine receptor antagonist hypothesis of antipsychotic drug action for positive symptoms of psychosis in the mesolimbic dopamine pathway is shown here. Blockade of postsynaptic dopamine 2 receptors by a dopamine 2 antagonist acting in the mesolimbic dopamine pathway is hypothesized to mediate the antipsychotic efficacy of the antipsychotic drugs and their ability to diminish or block positive symptoms. 

Antipsychotics have varying degrees of sedative properties. Contrary to previous beliefs, sedative properties do not enhance the antipsychotic efficacy of these drugs. Consequently, sedative side effects offer no benefit and can be detrimental in withdrawn psychotic patients. 

After the introduction of the first neuroleptic drugs, many animal models were developed to screen new compounds for potential antipsychotic activity. These models predict both antipsychotic efficacy and side effect liability in humans (104-106). Other animal models at-... 

A series of 6-aminoalkyltetrahydroindol-4-ones related to molindone (91) show potent affinities for D, and 5-HT receptors (610). Molindone exhibits many similarities to typical neuroleptics, including Dg antagonism, antipsychotic efficacy, and EPS (611). Zotepine (136) is a potent D, and 5-HT antagonist with high affinity for the 5-HT, receptor. 

Antipsychotics are the mainstay treatment for schizophrenia. There is large variability between individuals in their response to antipsychotics, both in efficacy and adverse effects of treatment. While the source of interindividual variability in antipsychotic response is not completely understood, genetics is a major contributing factor. The identification of pharmacogenetic markers that predict antipsychotic efficacy and adverse reactions is a growing area of research, and holds the potential to replace the current trial-and-error approach to treatment selection in schizophrenia with a personalized medicine approach. 

---