Differential regional and dose-related effects of asenapine on dopamine receptor subtypes

Abstract

These results indicate that asenapine has region-specific and dose-dependent effects on dopamine receptor subtypes in rat forebrain, which may contribute to asenapine's unique psychopharmacological properties.

Asenapine monotherapy in the acute treatment of both schizophrenia and bipolar I disorder

“…34,35 In addition, antagonism at 5HT 2A receptors, leading to an increase in dopamine activity in the prefrontal cortex, has also been suggested as a possible mechanism for alleviating negative symptoms 2,35 and enhancing cognition 36 in schizophrenia and other disorders. Findings from rat studies deduced that asenapine causes a dose-dependent increase in cortical 37 and hippocampal dopamine 37 , noradrenaline 38 and acetylcholine 38 comparable to previous reports with clozapine and quetiapine. Similarly, the 5HT 2C receptor may also have a similar role as 5HT 2A and its antagonism has been linked to improvement in negative symptoms.…”

Effects of asenapine, olanzapine, and risperidone on psychotomimetic-induced reversal-learning deficits in the rat

“…Asenapine was dissolved in 0.9% saline and administered subcutaneously (s.c.). Asenapine was given s.c. in an attempt to provide a surrogate for the sublingual route used in clinical studies [44], as well as for consistency with other preclinical studies that have assessed the effects of asenapine [15,23,53,54].…”

“…Based on preliminary tests with asenapine (0.003-0.1 mg/kg s.c.) that assessed effects on spontaneous locomotor activity, doses of asenapine (0.025, 0.05, and 0.075 mg/kg s.c.) were chosen that were expected to have minimal effects on motor function. The asenapine doses and s.c. route used in these studies were also based on studies demonstrating D 2 receptor occupancy in rat brain [46] and demonstrating antipsychotic-like activity in established neurochemical and behavioral paradigms [15,23,54]. Asenapine was administered 40 minutes before testing and 10 minutes before PCP or D-amphetamine.…”

Repeated effects of asenapine on adrenergic and cholinergic muscarinic receptors

“…The asenapine doses selected are active in neurochemical and behavioural paradigms and were used for comparison with those studies (Franberg et al 2008;Tarazi et al 2008Tarazi et al , 2009. Gross motoric or weight effects are not observed with this treatment paradigm.…”

“…Preclinical studies have demonstrated that asenapine blocks the conditioned avoidance response (predictive of antipsychotic activity) without inducing catalepsy (predictive of extrapyramidal side-effects) (Franberg et al 2008). Repeated treatment with asenapine alters densities of dopamine, serotonin, and glutamate receptor subtypes in a fashion similar to that of second-but not first-generation antipsychotic drugs (Tarazi et al 2008(Tarazi et al , 2009.…”