α2-Adrenoceptors are targets for antipsychotic drugs

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-HT_1A, 5-HT_2A, 5-HT_2C, 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, α_2A, α_2B and α_2C. Whereas the α_2B-adrenoceptor seems to play only a minor role in the brain, activation of postsynaptic α_2A-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 α_2C-adrenoceptor blockade or the combination of D₂ receptor antagonists with idazoxan (α_2A/2C-adrenoceptor antagonist) could be useful in schizophrenia. A potential benefit of a treatment combination of first-generation APDs with the α_2A/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.     

Complete response to therapy: why do primary central nervous system lymphoma patients not return to work?

Journal of Neuro-Oncology - Evidence supporting routine postoperative antiepileptic drug (AED) prophylaxis following oncologic neurosurgery is limited, and actual practice patterns are largely...     

Development of a new class of nonimidazole histamine H(3) receptor ligands with combined inhibitory histamine N-methyltransferase activity

In search of novel ways to enhance histaminergic neurotransmission in the central nervous system, a new class of nonimidazole histamine H(3) receptor ligands were developed that simultaneously possess strong inhibitory activity on the main histamine metabolizing enzyme, histamine N-methyltransferase (HMT). The novel compounds contain an aminoquinoline moiety, which is an important structural feature for HMT inhibitory activity, connected by different spacers to a piperidino group (for H(3) receptor antagonism). Variation of the spacer structure provides two different series of compounds. One series, having only an alkylene spacer between the basic centers, led to highly potent HMT inhibitors with moderate to high affinity at human histamine H(3) receptors. The second series possesses a p-phenoxypropyl spacer, which may be extended by another alkylene chain. This latter series also showed strong inhibitory activity on HMT, and in most cases, the H(3) receptor affinity even surpassed that of the first series. One of the most potent compounds with this dual mode of action is 4-(4-(3-piperidinopropoxy)phenylamino)quinoline (34) (hH(3), K(i) = 0.09 nM; HMT, IC(50) = 51 nM). This class of compounds showed high antagonist potency and good H(3) receptor selectivity in functional assays in guinea pig on H(1), H(2), and H(3) receptors. Because of low or missing in vivo activity of two selected compounds, the proof of concept of these valuable pharmacological tools for the supposed superior overall enhancing effect on histaminergic neurotransmission failed to appear hitherto.     

Increased level of polymerase Ⅲ transcribed Alu RNA in hepatocellular carcinoma tissue

There have been extensive observations that RNA containing repetitive elements accumulates in transformed cells and tumor tissues. In the present study, we first obtained result consistent with previous observations by in situ hybridization.     

Motor performance and functional ability in preschool- and early school-aged children with Juvenile Idiopathic Arthritis: a cross-sectional study

Objective  

To describe the level of motor performance and functional skills in young children with JIA.