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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. 相似文献13.
Further characterization of factor VIII-deficient mice created by gene targeting: RNA and protein studies 总被引:6,自引:7,他引:6
Bi L; Sarkar R; Naas T; Lawler AM; Pain J; Shumaker SL; Bedian V; Kazazian HH Jr 《Blood》1996,88(9):3446-3450
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Wiemann Greta Pertz Milena Kowalski Thomas Seidel Sabine Schlegel Uwe Thoma Patrizia 《Journal of neuro-oncology》2020,146(1):171-180
Journal of Neuro-Oncology - Evidence supporting routine postoperative antiepileptic drug (AED) prophylaxis following oncologic neurosurgery is limited, and actual practice patterns are largely... 相似文献
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Apelt J Ligneau X Pertz HH Arrang JM Ganellin CR Schwartz JC Schunack W Stark H 《Journal of medicinal chemistry》2002,45(5):1128-1141
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. 相似文献
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Tang RB Wang HY Lu HY Xiong J Li HH Qiu XH Liu HQ 《第二军医大学学报》2005,26(8):880-880
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. 相似文献
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Janjaap van der Net Patrick van der Torre Raoul HH Engelbert Vivian Engelen Femke van Zon Tim Takken Paul JM Helders 《Pediatric rheumatology online journal》2008,6(1):2