Design and synthesis of N‑(benzylpiperidinyl)‑4‑fluorobenzamide: A haloperidol analog that reduces neuropathic nociception via σ1 receptor antagonism

Publication date: Available online 23 January 2020Source: Life SciencesAuthor(s): Myrna Déciga-Campos, Luis Alberto Melo-Hernández, Héctor Torres-Gómez, Bernhard Wünsch, Dirk Schepmann, María Eva González-Trujano, Josué Espinosa-Juárez, Francisco Javier López-Muñoz, Gabriel Navarrete-VázquezAbstractAimsHaloperidol is a neuroleptic drug with high affinity towards the σ1 receptor (σ1R), acting as antagonist that decreases neuropathic pain, but has CNS side effects. This work describes the design and synthesis of a novel analog N‑(1‑benzylpiperidin‑4-yl)‑4‑fluorobenzamide (LMH-2), which produced antihyperalgesic and antiallodynic effects in rats with neuropathy induced by chronic constriction injury of the sciatic nerve (CCI), being more active than gabapentin (The most widely used drug for the treatment of neuropathic pain).Main methodsLMH-2 was designed as haloperidol analog. Its structure was characterized by spectroscopic (1H and 13C NMR) and spectrometric mass (electronic impact) techniques. Additionally, in silico predictions of pharmacokinetic, pharmacodynamic and toxicological properties were obtained, with promising results. A competitive binding assay using radioligands was employed to evaluate the in vitro affinity for σ1R, whereas in vivo antihyperalgesic and antiallodynic activities were investigated using Wistar rats with CCI.Key findingsLMH-2 showed high a...
Source: Life Sciences - Category: Biology Source Type: research

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CONCLUSIONS: We found DEGs and DEMs in FM patients through bioinformatics analysis, which may be involved in the occurrence and development of FM and serve as potential targets for diagnosis and treatment. PMID: 32083545 [PubMed - as supplied by publisher]
Source: Clinical and Experimental Rheumatology - Category: Rheumatology Tags: Clin Exp Rheumatol Source Type: research
Authors: Alikhajeh Y, Barabadi E, Mohammad Rahimi GR Abstract CONTEXT: In many societies, although chronic low back pain (LBP) is a significant problem, there is no consensus on the optimal therapeutic intervention. OBJECTIVE: To compare the impact of aquatic exercise (AE) and kinesio taping (KT) on the pain intensity and functional incapacity in women with chronic nonspecific LBP. DESIGN: Randomized controlled trial. SETTING: Outpatient clinic. PARTICIPANTS: Thirty-six women with chronic nonspecific LBP (mean [SD]: age = 50.69 [4.187] y) participated. INTERVENTIONS: Participants randomly a...
Source: Journal of Sport Rehabilitation - Category: Sports Medicine Tags: J Sport Rehabil Source Type: research
It’s been a while since I last posted on my blog, as I’ve had other projects on the go this summer. Over this time I’ve been pondering, as I usually do, why pain management/rehabilitation has so many problems. Conceptually, I can understand that pain is a complex experience that we’re a long way from understanding. I get that it’s a philosophically challenging subject. That because it’s subjective (like love, disgust, fatigue or hunger) it’s difficult to examine dispassionately. I also get that it’s big business. Pain is one aspect of being human that captures the entrepr...
Source: HealthSkills Weblog - Category: Anesthesiology Authors: Tags: Low back pain Pain conditions Professional topics Science in practice Source Type: blogs
Authors: Abstract Chronic pelvic pain is a common, burdensome, and costly condition that disproportionately affects women. Diagnosis and initial management of chronic pelvic pain in women are within the scope of practice of specialists in obstetrics and gynecology. The challenging complexity of chronic pelvic pain care can be addressed by increased visit time using appropriate coding modifiers, as well as identification of multidisciplinary team members within the practice or by facilitated referral. This Practice Bulletin addresses the diagnosis and management of chronic pelvic pain that is not completely explai...
Source: Obstetrics and Gynecology - Category: OBGYN Tags: Obstet Gynecol Source Type: research
Authors: Abstract Chronic pelvic pain is a common, burdensome, and costly condition that disproportionately affects women. Diagnosis and initial management of chronic pelvic pain in women are within the scope of practice of specialists in obstetrics and gynecology. The challenging complexity of chronic pelvic pain care can be addressed by increased visit time using appropriate coding modifiers, as well as identification of multidisciplinary team members within the practice or by facilitated referral. This Practice Bulletin addresses the diagnosis and management of chronic pelvic pain that is not completely explai...
Source: Obstetrics and Gynecology - Category: OBGYN Tags: Obstet Gynecol Source Type: research
In this study, olfactory ensheathing cells (OECs) were cultured, chitosan (CS) was prepared, and the compatibility of CS and OECs was detected by MTT method. Animal model of chronic constrictive sciatic nerve injury (CCI) was made, OECs and OECs+CS were transplanted to the region surrounding the chronic sciatic nerve injury, and the difference between the two groups in the treatment of NPP was compared. The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were measured by using behavioral method. In situ hybridization and Western-blotting were used to detect the expression of P2X4R mRNA and protei...
Source: Neuroscience Letters - Category: Neuroscience Source Type: research
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Source: International Journal of Surgery Case Reports - Category: Surgery Source Type: research
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Source: Journal of Psychosomatic Obstetrics and Gynaecology - Category: OBGYN Tags: J Psychosom Obstet Gynaecol Source Type: research
Every year in the United States, the CDC estimates that influenza results in between 9 million – 45 million illnesses, between 140,000 – 810,000 hospitalizations, and between 12,000 – 61,000 deaths (approximately 100  – 200 being pediatric fatalities). In the United States, the immense disease burden of the flu is unparalleled with any other pathogen, but fortunately there is a vaccine and antiviral medications which help to mitigate the yearly morbidity and mortality wrought by influenza.Because the flu changes its shape every year by a process called antigenic shift&n...
Source: A Pediatrician's Blog - Category: Pediatrics Source Type: blogs
ConclusionOur results demonstrate that either Endomorphin-1 or CGRP receptor antagonist is able to decrease the neuropathic pain after SCI but combination therapy by a CGRP receptor antagonist and Endomorphin-1 did not make any further reduction in pain sensation.
Source: Journal of Chemical Neuroanatomy - Category: Neuroscience Source Type: research
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