He also observed a contradiction in these personalities: on the one hand, they stubbornly hold on to their unusual ideas, on the other hand, they often accept every piece of gossip as the truth. Kraepelin also noted that paranoid personalities were often present in people who later developed paranoid psychosis. Subsequent writers also considered traits like suspiciousness and hostility to predispose people to developing delusional illnesses, particularly "late paraphrenias" of old age.Following Kraepelin, Eugen Bleuler described "contentious psychopathy" or "paranoid constitution" as displaying the characteristic triad of suspiciousness, grandiosity and feelings of persecution. He also emphasized that these peoples false assumptions do not attain the form of real delusion.Ernst Kretschmer emphasized the sensitive inner core of the paranoia-prone personality: they feel shy and inadequate but at the same time they have an attitude of entitlement. They attribute their failures to the machinations of others but secretly to their own inadequacy. They experience constant tension between feelings of self-importance and experiencing the environment as unappreciative and humiliating.Karl Jaspers, a German phenomenologist, described "self-insecure" personalities who resemble the paranoid personality. According to Jaspers, such people experience inner humiliation, brought about by outside experiences and their interpretations of them. They have an urge to get external confirmation to their self-deprecation and that makes them see insults in the behavior of other people. They suffer from every slight because they seek the real reason for them in themselves.
Lurbinectedin, sold under the brand name Zepzelca, is a medication used for the treatment of small cell lung cancer.The most common side effects include leukopenia, lymphopenia, fatigue, anemia, neutropenia, increased creatinine, increased alanine aminotransferase, increased glucose, thrombocytopenia, nausea, decreased appetite, musculoskeletal pain, decreased albumin, constipation, dyspnea, decreased sodium, increased aspartate aminotransferase, vomiting, cough, decreased magnesium and diarrhea.Lurbinectedin is a synthetic tetrahydropyrrolo [4,3,2-de]quinolin-8(1H)-one alkaloid analogue with potential antineoplastic activity. Lurbinectedin covalently binds to residues lying in the minor groove of DNA, which may result in delayed progression through S phase, cell cycle arrest in the G2/M phase and cell death.Lurbinectedin was approved for medical use in the United States in June 2020. Medical uses
Lurbinectedin is indicated for the treatment of adults with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy. Structure
Lurbinectedin is structurally similar to trabectedin, although the tetrahydroisoquinoline present in trabectedin is replaced with a tetrahydro β-carboline which enables lurbinectedin to exhibit increased antitumor activity compared with trabectedin. Synthesis
Synthesis of lurbinectedin starts from small, common starting materials that require twenty-six individual steps to produce the drug with overall yield of 1.6%. Mechanism of action
According to PharmaMar, lurbinectedin inhibits the active transcription of the encoding genes. This has two consequences. It promotes tumor cell death and normalizes the tumor microenvironment. Active transcription is the process by which there are specific signal where information contained in the DNA sequence is transferred to an RNA molecule. This activity depends on the activity of an enzyme called RNA polymerase II.