Clozapine, ziprasidone and aripiprazole but not haloperidol protect against kainic acid-induced lesion of the striatum in mice, in vivo: Role of 5-HT1A receptor activation

Effects of chronic oral treatment with aripiprazole on the expression of NMDA receptor subunits and binding sites in rat brain

“…We propose a regulation of NMDA-R expression via intra-and intercellular pathways after dopaminergic D1 and D2 and serotonergic 5HT1A receptor activation (Bruins Slot et al 2005;Nagai et al 2009). This corresponds to reports that the 5HT1A agonism of APZ facilitates the rescue of PCP-and MK801-induced behavioral effects (Cosi et al 2005;Nagai et al 2009;Snigdha and Neill 2008). In addition, the agonism at D1 receptors and APZ-induced dopamine release (Li et al 2004) seems important because a stimulation of D1 receptors potentiated NMDA currents in rat PFC (Wirkner et al 2004), improved PCP-induced cognitive deficits (McLean et al 2009), and blocked PCP-induced neurotoxicity (Lei et al 2009).…”

“…As a first hint towards pro-glutamatergic effects, APZ was recently shown to suppress the expression of glutamate transporter genes (Segnitz et al 2009). In behavioral animal models, APZ exerted anxiolytic effects (Dahan et al 2009), protected against kainic acid-induced lesions (Cosi et al 2005), and also reversed PCP-induced deficits of social interaction (Snigdha and Neill 2008). In each assessment, APZ-inherent 5-HT1A agonism was found crucial.…”

Interaction of the novel antipsychotic aripiprazole with 5-HT1A and 5-HT2A receptors: functional receptor-binding and in vivo electrophysiological studies

“…Antagonist activity at postsynaptic 5-HT 1A receptors was associated with anxiolytic activity and improvements in cognitive functioning (Millan 2000). Of interest, a recent preclinical study showed the neuroprotective effects of 5-HT 1A agonism by aripiprazole (Cosi et al 2005). This neuroprotective action may contribute to the novel mode of action of aripiprazole.…”

Pharmacological and Nonpharmacological Management of Delirium in Critically Ill Patients

“…Atypical anti-psychotics are distinguished from the neuroleptic anti-psychotics, such as haloperidol, due to their reduced affinity for dopamine receptors, particularly D 2 receptors, and they also have a wider variety of reported affinities for other central nervous system receptors, including serotonin, adrenergic, and muscarinic receptors [79,83]. For example, an atypical anti-psychotic named ziprasidone is an antagonist at D 2 , H 1 , α 1 , 5-HT 2A , 5-HT 2C , and 5-HT 1D and an agonist at 5-HT 1A receptors [79,81,83,84]. A high 5-HT 2A /D 2 receptor affinity ratio, which is a particularly strong characteristic of ziprasidone, has been correlated with lower propensity for extrapyramidal symptoms (EPS) and may be advantageous in treating the negative symptoms so prevalent in older hypoactive delirious patients [24,85].…”