Differential region-specific regulation of central ?1-adrenoceptor binding following chronic haloperidol and clozapine administration in the rat

Abstract

Central alpha(1)-adrenoceptors are differentially regulated after chronic haloperidol and clozapine treatment. It is suggested that thalamic alpha(1)-adrenoceptors may represent a common anatomical locus contributing to the antipsychotic activity and/or alpha(1)-adrenoceptor centrally mediated side effects of both drugs, whereas the selective upregulation of cortical alpha(1)-adrenoceptor density by clozapine may contribute, in part, to its superior atypical properties.

Cardiac and neuroprotection regulated by α1-adrenergic receptor subtypes

“…Many sources cite the antagonism of the α 1A -AR subtype as mediating this antipsychotic action though the data may not support this claim sufficiently, as the conclusions were based on studies performed in the peripheral nervous system while studying side effects (183) or not actually focused on the α 1 -AR subtypes (184). The binding affinities of clozapine for α 1A - and α 1B -ARs are not significantly different (185,186); however, the observed α 1 -AR up-regulation that occurs with clozapine treatment is mainly in areas of high α 1B -AR expression (187). In addition, the atypical antipsychotic risperidone has 120-fold antagonist selectivity for the α 1B -AR in the hippocampus (185).…”

Dissimilar effects of subchronic clozapine and haloperidol on operant lever pressing in C57BL/6J, BALB/cJ, and LP/J mice

“…Tolerance to the rate-suppressing effect of clozapine in BALB/cJ mice might be a reflection of the upregulation of a 1 noradrenergic receptors, as these proteins have been observed to be upregulated in the rat brain in response to 21-day treatment with clozapine (Cahir et al, 2004). An increase in a 1 receptor density would be consistent with a diminishing effect of clozapine as dosing continued, because clozapine has pronounced a 1 antagonist effects (Schotte et al, 1996).…”

Repeated effects of asenapine on adrenergic and cholinergic muscarinic receptors

“…A previous study reported increases in frontal cortex 3 wk after clozapine administration (Cahir et al 2004). As such, it could be speculated that newer antipsychotics with the ability to block a 1 receptors would also increase cortical a 1 -receptor binding.…”