Neue potentielle pharmakologische Behandlung bei Alkoholabhängigkeit im transnationalen Forschungsansatz entdeckt: Neurokinin-1 Rezeptor Antagonist als mögliche Therapie der Alkoholabhängigkeit?

2008 ◽  
Author(s):  
J. Mutschler ◽  
M. Grosshans ◽  
F. Kiefer
Keyword(s):  
Neurokinin 1 ◽  
Pharmakologische Behandlung

Modulation of Stress- and Inflammation induced Visceral Hypersensitivity by peripheral Neurokinin 1 Receptors

2005 ◽  
Vol 43 (05) ◽  
Author(s):  
T Liebregts ◽  
B Adam ◽  
C Schneider ◽  
J Carri ◽  
A Bertel ◽  
...  
Keyword(s):  
Visceral Hypersensitivity ◽  
Neurokinin 1

Insight into Pain Modulation: Nociceptors Sensitization and Therapeutic Targets

2019 ◽  
Vol 20 (7) ◽  
pp. 775-788 ◽  
Author(s):  
Amna Khan ◽  
Salman Khan ◽  
Yeong Shik Kim
Keyword(s):  
Ion Channels ◽  
Cannabinoid Receptors ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Experimental Models ◽  
Pain Modulation ◽  
Metabotropic Glutamate ◽  
Pain Sensitization ◽  
Neurokinin 1 ◽  
Pain Transduction

Pain is a complex multidimensional concept that facilitates the initiation of the signaling cascade in response to any noxious stimuli. Action potential generation in the peripheral nociceptor terminal and its transmission through various types of nociceptors corresponding to mechanical, chemical or thermal stimuli lead to the activation of receptors and further neuronal processing produces the sensation of pain. Numerous types of receptors are activated in pain sensation which vary in their signaling pathway. These signaling pathways can be regarded as a site for modulation of pain by targeting the pain transduction molecules to produce analgesia. On the basis of their anatomic location, transient receptor potential ion channels (TRPV1, TRPV2 and TRPM8), Piezo 2, acid-sensing ion channels (ASICs), purinergic (P2X and P2Y), bradykinin (B1 and B2), α-amino-3-hydroxy-5- methylisoxazole-4-propionate (AMPA), N-methyl-D-aspartate (NMDA), metabotropic glutamate (mGlu), neurokinin 1 (NK1) and calcitonin gene-related peptide (CGRP) receptors are activated during pain sensitization. Various inhibitors of TRPV1, TRPV2, TRPM8, Piezo 2, ASICs, P2X, P2Y, B1, B2, AMPA, NMDA, mGlu, NK1 and CGRP receptors have shown high therapeutic value in experimental models of pain. Similarly, local inhibitory regulation by the activation of opioid, adrenergic, serotonergic and cannabinoid receptors has shown analgesic properties by modulating the central and peripheral perception of painful stimuli. This review mainly focused on various classes of nociceptors involved in pain transduction, transmission and modulation, site of action of the nociceptors in modulating pain transmission pathways and the drugs (both clinical and preclinical data, relevant to targets) alleviating the painful stimuli by exploiting nociceptor-specific channels and receptors.

scholarly journals Need for Flexible Adjustment of the Treatment Schedule for Aprepitant Administration against Erlotinib-Induced Refractory Pruritus and Skin Rush

2019 ◽  
Vol 12 (1) ◽  
pp. 84-90 ◽  
Author(s):  
Nobuhiko Seki ◽  
Ryosuke Ochiai ◽  
Terunobu Haruyama ◽  
Masashi Ishihara ◽  
Maika Natsume ◽  
...  
Keyword(s):  
Substance P ◽  
Kinase Inhibitor ◽  
Growth Factor Receptor ◽  
Stage Iv ◽  
Subsequent Treatment ◽  
Treatment Schedule ◽  
Weekly Schedule ◽  
Patient Centered ◽  
Neurokinin 1 ◽  
Dermatological Side Effects

Common dermatological side-effects associated with erlotinib, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), include pruritus and skin rash, which are mediated by substance P, leading to the occasional discontinuation of cancer treatment. Aprepitant is an antagonist of neurokinin-1 receptor, through which substance P activates the pruritogens. Thus, aprepitant is expected to offer a promising option for the treatment of erlotinib-induced pruritus. However, the appropriate treatment schedule for aprepitant administration is under consideration. Here, we discuss the need for flexible adjustment of the treatment schedule for aprepitant administration against erlotinib-induced refractory pruritus and skin rush. A 71-year-old female smoker presented with stage IV EGFR-mutated lung adenocarcinoma. She was started on erlotinib at 150 mg/day. However, by 28 days, severe pruritus and acneiform skin rush resistant to standard therapies occurred, resulting in the interruption of erlotinib therapy. After recovery, she was restarted on erlotinib at 100 mg/day. However, severe pruritus and skin rush developed again within 2 weeks. Then, we started the first 3-day dose of aprepitant (125 mg on day 1, 80 mg on day 3, and 80 mg on day 5) based on the results of the previous prospective study, which showed the success rate of 100% with at least the second dose of aprepitant. However, the pruritus and skin rush exacerbated again within 4 weeks. Therefore, we started the second 3-day dose of aprepitant, but in vain. At this point, as the patient-centered medicine, bi-weekly schedule of the 3-day dose of aprepitant was considered and, then, adopted. As the results, the pruritus and skin rush remained well-controlled throughout the subsequent treatment with erlotinib.

scholarly journals JAK-Inhibitoren für die Behandlung hämatoonkologischer Erkrankungen

2020 ◽  
Vol 45 (06) ◽  
pp. 559-567
Author(s):  
Torsten Steinbrunn ◽  
Josip Zovko ◽  
Sabrina Kraus
Keyword(s):  
Phase Iii ◽  
Polycythaemia Vera ◽  
Jak Inhibitor ◽  
Graft Versus Host ◽  
Pharmakologische Behandlung

ZusammenfassungDie konstitutive Aktivierung des JAK-STAT-Signalwegs ist charakteristisch für die Pathogenese der myeloproliferativen Neoplasien, speziell der primären Myelofibrose, der Polycythaemia vera und der essentiellen Thrombozythämie. Die Einführung von oral verfügbaren JAK-Inhibitoren in die Klinik brachte einen entscheidenden Fortschritt für die pharmakologische Behandlung der Myelofibrose und der Polycythaemia vera, wenngleich damit noch keine Heilung verbunden ist. Im Vordergrund steht die Verbesserung der Lebensqualität der meist älteren Patienten durch Kontrolle krankheitsbedingter konstitutioneller Symptome, Reduktion einer bestehenden Splenomegalie und Vermeidung insbesondere von thromboembolischen Folgekomplikationen. Darüber hinaus kann die Therapie von Myelofibrose-Patienten mit JAK-Inhibitoren jedoch auch deren Krankheitsverlauf verlangsamen und ihr Gesamtüberleben verlängern. Der bislang einzige in Europa zugelassene JAK-Inhibitor Ruxolitinib hemmt die Isoformen JAK1 und JAK2 und besitzt sowohl antiinflammatorisches als auch antiproliferatives Potenzial. Damit zeigt dieser Inhibitor überdies eine gute Wirkung in der Therapie der Graft-versus-Host-Erkrankung nach allogener hämatopoetischer Stammzelltransplantation. Mit Fedratinib, Pacritinib und Momelatinib befinden sich derzeit 3 weitere vielversprechende JAK-Inhibitoren mit etwas unterschiedlichen Wirkprofilen in der klinischen Phase III-Testung. Diese zeigen auch bei Patienten mit unwirksamer oder unverträglicher Vorbehandlung mit Ruxolitinib Wirksamkeit, sodass eine kontinuierliche Weiterentwicklung der entsprechenden Therapiestrategien abzusehen ist.

scholarly journals OTHR-16. CONCURRENT USE OF APREPITANT AND IFOSFAMIDE IN PEDIATRIC CANCER PATIENTS

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii424-iii424
Author(s):  
Shelby Winzent ◽  
Nathan Dahl ◽  
Molly Hemenway ◽  
Rachel Lovria ◽  
Kathleen Dorris
Keyword(s):  
Germ Cell ◽  
Germ Cell Tumors ◽  
Hepatic Metabolism ◽  
High Dose ◽  
Tumor Type ◽  
Age Related ◽  
Concurrent Use ◽  
Pediatric Cancer Patients ◽  
Nongerminomatous Germ Cell Tumor ◽  
Neurokinin 1

Abstract BACKGROUND Aprepitant, a selective neurokinin-1 receptor antagonist, is commonly used for prevention of chemotherapy-induced nausea and vomiting. Its use with ifosfamide is controversial due to the putative risk of potentiating neurotoxicity via inhibition of cytochrome P450 3A4 (CYP3A4). The current literature examining this interaction is inconclusive, and little data exists in pediatrics. We seek to describe a single-institution experience with concurrent aprepitant and ifosfamide administration. METHODS A retrospective review of patients treated with ifosfamide and aprepitant from 2009–2018 was conducted. Data collected included demographics, tumor type, number of days of concurrent therapy, dosing, and documented of neurotoxicity. RESULTS Twenty patients aged 7–21 years (median 17 years) were identified. Diagnoses included thirteen sarcomas and seven CNS tumors (6 germ cell tumors; 1 intracranial sarcoma). Five patients received high dose ifosfamide (>2,000mg/m2/day). The number of concurrent ifosfamide and aprepitant doses ranged from 2–18 (median, 8.5). Only one patient (5%) developed ifosfamide-induced neurotoxicity: a 7-year-old female with a nongerminomatous germ cell tumor who presented with seizures and somnolence. She received methylene blue and returned to her neurologic baseline. She completed her ifosfamide course without incident. She was the only patient to require weight-based aprepitant dosing and to receive the liquid formulation. CONCLUSIONS Aprepitant should be used with caution when administered concurrently with ifosfamide due to the risk of neurotoxicity. However, the incidence of neurotoxicity in this retrospective pediatric cohort was low. This interaction may be more significant in younger patients due to age-related differences in hepatic metabolism, but further study is required.

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