Prolactin and antipsychotic medications: mechanism of action

The effects of olanzapine and fluphenazine on plasma cortisol, prolactin and muscle rigidity in schizophrenic patients: A double blind study

“…Hyperprolactinemia is a common side effect of typical antipsychotics Petty, 1999), while atypical antipsychotics especially olanzapine, are PRL-sparing drugs (Dickson and Glazer, 1999). In our study fluphenazine induced more pronounced PRL increase than olanzapine.…”

Characterization of Inhibition by Risperidone of the Inwardly Rectifying K+ Current in Pituitary GH3 Cells

“…Risperidone, like most neuroleptic drugs, has been recognized to interfere with the actions of dopamine as a neurotransmitter, particularly at D 2 and D 2 -like receptors (Petty 1999;Vanhauwe et al 1999). However, it seems unlikely that the effect of risperidone on I K(IR) observed in GH 3 cells is primarily due to its activity as an antagonist to dopamine D 2 receptors.…”

“…Metoclopramide was also reported to antagonize at dopamine receptor; 2) in GH 3 cells preincubated with dopamine (10 M), the inhibitory effect of risperidone on I K(IR) was unaffected; and 3) risperidone at a higher concentration (10 M) applied intracellularly also suppressed the activity of BK Ca channels. Therefore, the carefulness may need to be made in ascribing the risperidone-mediated prolactin release to those caused by the blockade of dopamine receptors in vivo or in vitro (Bowden et al 1992;Breier et al 1999;Kim et al 1999;Petty 1999;Carboni et al 2000).…”

“…The most significant and consistent neuroendocrine effect of neuroleptic drugs is to stimulate prolactin secretion and cause galactorrhea, although these adverse effects vary greatly in potency and chemical structure (Bowden et al 1992;Popli et al 1998;Breier et al 1999;Kleinberg et al 1999;Petty 1999). This important site of action has been thought to be primarily due to the blockade of dopamine D 2 receptors (Popli et al 1998;Kapur et al 1999;Kim et al 1999;Petty, 1999;Vanhauwe et al 1999). On the other hand, recent evidence suggests that these neuroleptics, including risperidone, may cause a significant prolongation of electrocardiographic QT interval (Drici et al 1998).…”

The substituted benzamides and their clinical potential on dysthymia and on the negative symptoms of schizophrenia

“…2 If only these two criteria were to be applied, then atypicals were already present since the early 1970s, when clozapine and most substituted benzamides were on the market. If instead three additional criteria, with less consensus in the literature-such as a decreased, or non-existent, capacity to induce hyperprolactinemia, 3 weight gain 4,5 and better effectiveness in some patients previously regarded as treatment-refractory 6 would be stringently added as essential features in the atypical profile of an antipsychotic, then most of the 'new' antipsychotics could not be considered atypicals.…”