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Yıl:1999; Cilt: 9; Sayı: 1>> Özet
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Klinik Psikofarmakoloji Bülteni; 1999;9(1):1-13
"Atipik antipsikotik" kavramı ve şizofreninin ilaçla tedavisinde yeni ufuklar
I Tuğlular
Ege Üniv. İlaç Geliştirme ve Farmakokinetik Araştırma Uygulama Merkezi, İzmir
Konvansiyonel antipsikotik ajanlar "nöroleptikler" olarak bilinir ve mezolimbik dopamin yolaklarındaki dopamin-2 reseptörlerini bloke ederek şizofreninin pozitif semptomlarını azaltırlar. Bu ajanlar aynı zamanda, ekstrapiramidal sistemdeki dopamin-2 reseptörlerini de bloke ederler. Genel olarak, "nöroleptik" terimi hem ekstrapiramidal hem de antipsikotik etkilere neden olan tüm ilaçlara atfen kullanılır. Geçen 10 yıl boyunca, araştırmalar daha iyi terapötik profili olan (örneğin, hem pozitif hem de negatif semptomlara etkili ve azalmış yan etkileri olan) bileşikler geliştirmeye odaklanmıştır. Bu bileşikler-klozapin bu bileşiklerin prototipik örneği olarak değerlendirilir-"atipik antipsikotik" olarak adlandırılır. Klasik olanlarla karşılaştırıldığında atipik antipsikotikler daha yüksek D2 reseptör seçiciliğine (sülpirid gibi); daha yüksek D1 reseptör seçiciliğine (klozapin gibi); 5-HT2 reseptör affinitesi ve antagonist etkiye (klozapin, melperon, setoperon, tiaspiron gibi); mezolimbik sistem veya nükleus akumbens üzerine seçici olarak etkili olma özelliğine (remoksiprid, rakloprid gibi); bir parsiyel agonist olarak postsinaptik etkiye (SDZ 208-911 gibi) ve presinaptik agonist (BHT 920 gibi) ya da antagonist (sülpirid gibi) olarak seçici etkiye sahiptir. Geleneksel ve atipik antipsikotik ilaçların etkinliği göz önüne alındığında, yeni bir sınıflandırma tanımlamak gerekmektedir. Aşağıdaki sınıflandırma önerilebilir: 1) Sedatif-antimanik antipsikotik ilaçlar; 2) Antiprodüktif antipsikotik ilaçlar ve 3) Psiko-reorganizatör antipsikotik.

Atypical antipyschotic concept and new horizons in drug treatment of schizophrenia
Conventional antipsychotic agents are known as neuroleptics, and these drugs block dopamine-2 receptors in the mesolimbic dopamine pathway in order to reduce positive symptoms of schizophrenia. These agents also block dopamine-2 receptors in extrapyramidal system. Generally, the term "neuroleptic" is applied to all drugs that produce both extrapyramidal and antipsychotic effects. During the past decade, the researches has focused on compounds with an improved therapeutic profile (i.e. improved efficacy on both positive and negative symptoms and decreased side effects). These compounds, of which clozapine is considered the prototypical agent, have been termed "atypical antipsychotics." Compared to classic neuroleptics atypical ones has a high selectivity for D2 receptors (e.g. sulpiride); a high selectivity for D1 receptors (e.g. clozapine); affinity for 5HT2 receptors and antagonist effect (e.g. clozapine, melperon, setoperon, tiaspiron); to act selectively on mesolimbic system or nucleus accumbens (e.g. remoxypride, raclopride); postsynaptic effect as an partial agonist (e.g. SDZ 208-911); and a selective effect as presynaptic agonist (e.g. BHT 920) or as antagonist (e.g. sulpiride). When the efficacy of traditional and atypical antipsychotics are considered, it is necessary to describe a new classification. The following classification may be suggested: 1) Sedative-antimanic neuroleptics; 2) Antiproductive neuroleptics; and 3) Psycho-reorganizatory neuroleptics.

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