α2-Adrenoceptors are targets for antipsychotic drugs.

Abstract

RATIONALE:

Almost all antipsychotic drugs (APDs), irrespective of whether they belong to the first-generation (e.g. haloperidol) or second-generation (e.g. clozapine), are dopamine D2 receptor antagonists. Second-generation APDs, which differ from first-generation APDs in possessing a lower propensity to induce extrapyramidal side effects, target a variety of monoamine receptors such as serotonin (5-hydroxytryptamine) receptors (e.g. 5-HT1A, 5-HT2A, 5-HT2C, 5-HT6, 5-HT7) and α1- and α2-adrenoceptors in addition to their antagonist effects at D2 receptors.

OBJECTIVE:

This short review is focussed on the potential role of α2-adrenoceptors in the antipsychotic therapy.

RESULTS:

Schizophrenia is characterised by three categories of symptoms: positive symptoms, negative symptoms and cognitive deficits. α2-Adrenoceptors are classified into three distinct subtypes in mammals, α2A, α2B and α2C. Whereas the α2B-adrenoceptor seems to play only a minor role in the brain, activation of postsynaptic α2A-adrenoceptors in the prefrontal cortex improves cognitive functions. Preclinical models such as D-amphetamine-induced locomotion, the conditioned avoidance response and the pharmacological N-methyl-D-aspartate receptor hypofunction model have shown that α2C-adrenoceptor blockade or the combination of D2 receptor antagonists with idazoxan (α2A/2C-adrenoceptor antagonist) could be useful in schizophrenia. A potential benefit of a treatment combination of first-generation APDs with the α2A/2C-adrenoceptor antagonists idazoxan or mirtazapine was also demonstrated in patients with schizophrenia.

CONCLUSIONS:

It is concluded that α2-adrenoceptors may be promising targets in the antipsychotic therapy.

• Authors: Jan Brosda, Florian Jantschak, Heinz H Pertz
• Journal: Psychopharmacology (Psychopharmacology (Berl)) Vol. 231 Issue 5 Pg. 801-12 (Mar 2014) ISSN: 1432-2072 [Electronic] Germany
• PMID: 24488407 (Publication Type: Journal Article, Review)

Chemical References

• Adrenergic alpha-2 Receptor Antagonists
• Antipsychotic Agents
• Receptors, Adrenergic, alpha-2

Topics

• Adrenergic alpha-2 Receptor Antagonists (pharmacology)
• Animals
• Antipsychotic Agents (pharmacology)
• Humans
• Molecular Targeted Therapy
• Receptors, Adrenergic, alpha-2 (metabolism)
• Schizophrenia (drug therapy, metabolism)