Exploitation of anti-amnesic drugs based on novel lead substance

由于老年人的人口增加，预防或改善新药物的剥削也是非常值得期待的。我们发现了三种类型的肽具有反健忘症或记忆增强的活动，补充系统被认为只具有免疫学意义。我们发现了Casoxin C，补充C3 a从Casein Digest中提取出来，补充C3 a本身增强了氨酰胺注射后的注射或脑细胞化学（icv.）老鼠的管理。这些肽在口头行政管理后是有害的。口服活性的C3 A抗药者WPLPR是根据YPLPR设计的，对五肽在雷扎坦素的羧基终止剂，对C3 A抗药者从大米专辑中提取出来的。δ-阿片类肽被报告用于学习不受阻碍。However， gluten exorphin A（GYYPT）， a δ-一种阿片类动物是从热谷氨酰胺的酶分类中分离出来的，在老鼠的口头管理后推广学习。[D-Ala] D1-gluten exorphin大约有60个比原来的肽多掉了。The dose for promotion of learning by these peptides were lower than that for analgesia.Nociceptin is a hyperalgesic peptide isolated from brain。早些时候，我们发现了一种反乌托邦肽具有反乌托邦拮抗剂活动的甲基化剂。我们最近发现了一项研究，即retronoceptin methylester具有noceptin拮抗剂活性。它还展示了模拟和记忆增强的活动。行政管理。Retronoceptin methylester可以被归类为一种理想的过敏药物的主要优点，因为它没有诱导性和对吗啡的记忆的影响，我们还发现了内源性肽、肠抑素（VPDPR）和前列腺激素N-终端20肽（PAMP）具有记忆增强和抗氨活性，因此，在ICV后也可以看到。行政管理。

As the population of aged people increases, exploitation of new drugs preventing or improving amnesia is eagerly expected. We found that three types of peptides had anti-amnesic or memory-enhancing activity.Complement system has been recognized to have only immunological importance. We found that casoxin C, complement C3a agonist derived from casein digest, and complement C3a itself improved amnesia induced by scopolamine injection or brain ischemia after intracerebroventricular(icv.)administration in mice. These peptides were ineffective after oral administration. Orally active C3a agonist WPLPR was designed based on YPLPR, which corresponds to the pentapeptide at the carboxyl terminus of oryzatensin, a C3a agonist derived from rice albumin.δ-Opioid peptides have been reported to inhibit learning. However, gluten exorphin A(GYYPT), a δ-opioid which was isolated from enzymatic digest of wheat gluten, promoted learning after oral administration in mice. [D-Ala]ィイD11ィエD1-gluten exorphin A was about 60 fold more potent than the original peptide. The dose for promotion of learning by these peptides were lower than that for analgesia.Nociceptin is a hyperalgesic peptide isolated from brain. Previously, we found that methylester of retro-opioid peptides had opioid antagonist activity. We newly found that retronociceptin methylester had nociceptin antagonist activity in guinea-pig ileum assay. It also showed analgesic and memory-enhancing activities icv. administration. Retronociceptin methylester can be regarded as a lead sunstance for an ideal analgesic drugs because it did not induce torelance and memory impairment which are characteristic for morphin.We also found that endogenous peptides, enterostatin(VPDPR)and proadrenomedullin N-terminal 20 peptde(PAMP)had memory-enhancing and antiamnesic activities, respectively, after icv. administration.