Synthesis and Antinociceptive activity of Newly Modified Amine analogs of Phencyclidine in Mice

2021 ◽  
Vol 25 ◽  
Author(s):  
Maryam Shokrollahi ◽  
Marjaneh Samadizadeh ◽  
Mohsen Khalili ◽  
Seyed Ali Sobhanian ◽  
Abbas Ahmadi
Keyword(s):  
Dipole Moments ◽  
Immersion Test ◽  
Piperidine Ring ◽  
Strong Electron ◽  
Tail Immersion ◽  
The Central Nervous System ◽  
Specific Receptors ◽  
Psychotomimetic Drugs ◽  
Analgesic Activities ◽  
New Compounds

Background: Phencyclidine (PCP, I) and its substituted analogs are significant and broadly abused psychotomimetic drugs that affect the central nervous system. They show many pharmacological properties due to the presence of specific receptors in the brain. Aim and Objective: Methyl group, despite strong electron-donating and characters of dipole moments, were placed on various positions of phenyl and amine moieties of Phencyclidine along with the substitution of benzylamine, piperazine, and aniline derivatives in place of piperidine ring of Phencyclidine to create novel compounds of the core with analgesic properties. Material and methods: For evaluation of the Analgesic activities of newly synthesized compounds, they were screened by tests of tail immersion (thermal) and formalin (chemical) pains. The obtained data with the control and PCP groups were compared too. Results: The outcomes indicated that some new compounds have more antinociceptive effects than PCP in tail immersion and formalin tests. In the tail immersion test, the methyl piperazine analog (III) shows more efficacy than others. In the formalin test, none of the compounds are as effective as phencyclidine at the earliest time-point, but compounds IV and V do show more effective during the second stage of formalin pain. Conclusion: It can be concluded that the methyl-piperazine analog of phencyclidine was the best candidate to decrease acute thermal and benzylamine derivatives were suitable candidates to reduce chemical pains.

New Amine and Aromatic Substituted Analogues of Phencyclidine: Synthesis and Determination of Acute and Chronic Pain Activities

2019 ◽  
Vol 22 (8) ◽  
pp. 570-576
Author(s):  
Maryam Shokrollahi ◽  
Marjaneh Samadizadeh ◽  
Mohsen Khalili ◽  
Seyed A. Sobhanian ◽  
Abbas Ahmadi
Keyword(s):  
Nmda Receptors ◽  
Phenyl Ring ◽  
Piperidine Ring ◽  
Methyl Group ◽  
Physiological Properties ◽  
Antinociceptive Effects ◽  
The Central Nervous System ◽  
Analgesic Activities ◽  
Compound Ii ◽  
New Compounds

Background: Phencyclidine (PCP, I) is a synthetic drug with remarkable physiological properties. PCP and its analogues exert many pharmacological activities and interact with some neurotransmitter systems in the central nervous system like particular affinity for PCP sites in NMDA receptors or dopamine uptake blocking or even both. Aim and Objective: The following research, methyl group with electron-donating and dipole moment characters was added in different positions of phenyl ring along with the substitution of benzylamine (with many pharmacological effects) instead of piperidine ring of I to produce new compounds (II-V) of this family with more analgesic activities. Materials and Methods: Analgesic activities of these new compounds were measured by tail immersion and formalin tests for acute and chronic pains, respectively. Also, the outcomes were compared with control and PCP (10 mg/kg) groups. Results: The results indicate that compounds III, IV, and V have more acute and chronic antinociceptive effects than PCP and compound II which may be concerned with more antagonizing activities of these new painkillers for the blockage of dopamine reuptake as well as high affinity for NMDA receptors PCP binding site. Conclusion: It can be concluded that the benzylamine derivative of phencyclidine with a methyl group on the benzyl position on phenyl ring (V) is a more appropriate candidate to reduce acute and chronic (thermal and chemical) pains compared to other substituted phenyl analogs (II-IV) and PCP.

scholarly journals 5-HT1A Serotonergic, α-Adrenergic and Opioidergic Receptors Mediate the Analgesic Efficacy of Vortioxetine in Mice

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3242
Author(s):  
Nazlı Turan Yücel ◽  
Ümmühan Kandemir ◽  
Ümide Demir Özkay ◽  
Özgür Devrim Can
Keyword(s):  
Analgesic Activity ◽  
Time Course ◽  
Motor Coordination ◽  
Antidepressant Drug ◽  
Area Under The Curve ◽  
Analgesic Efficacy ◽  
Synthesis Inhibitor ◽  
Tail Immersion ◽  
Adrenoceptor Blocker ◽  
The Central Nervous System

Vortioxetine is a multimodal antidepressant drug that affects several brain neurochemicals and has the potential to induce various pharmacological effects on the central nervous system. Therefore, we investigated the centrally mediated analgesic efficacy of this drug and the mechanisms underlying this effect. Analgesic activity of vortioxetine (5, 10 and 20 mg/kg, p.o.) was examined by tail-clip, tail-immersion and hot-plate tests. Motor performance of animals was evaluated using Rota-rod device. Time course measurements (30–180 min) showed that vortioxetine (10 and 20 mg/kg) administrations significantly increased the response latency, percent maximum possible effect and area under the curve values in all of the nociceptive tests. These data pointed out the analgesic effect of vortioxetine on central pathways carrying acute thermal and mechanical nociceptive stimuli. Vortioxetine did not alter the motor coordination of mice indicating that the analgesic activity of this drug was specific. In mechanistic studies, pre-treatments with p-chlorophenylalanine (serotonin-synthesis inhibitor), NAN-190 (serotonin 5-HT1A receptor antagonist), α-methyl-para-tyrosine (catecholamine-synthesis inhibitor), phentolamine (non-selective α-adrenoceptor blocker), and naloxone (non-selective opioid receptor blocker) antagonised the vortioxetine-induced analgesia. Obtained findings indicated that vortioxetine-induced analgesia is mediated by 5-HT1A serotonergic, α-adrenergic and opioidergic receptors, and contributions of central serotonergic and catecholaminergic neurotransmissions are critical for this effect.

scholarly journals Bioactivities of the ethanol extract from Ageratum fastigiatum branches: antioxidant, antinociceptive and anti-inflammatory

2016 ◽  
Vol 88 (3) ◽  
pp. 1471-1484
Author(s):  
GLAUCIEMAR DEL-VECHIO-VIEIRA ◽  
BRUNA C.S. SANTOS ◽  
MARIA SILVANA ALVES ◽  
AÍLSON L.A. ARAÚJO ◽  
CÉLIA H. YAMAMOTO ◽  
...  
Keyword(s):  
Antinociceptive Effect ◽  
Folk Medicine ◽  
Reducing Power ◽  
Ethanol Extract ◽  
Immersion Test ◽  
Significant Inhibition ◽  
Paw Edema ◽  
Hot Plate ◽  
Tail Immersion ◽  
Anti Inflammatory

ABSTRACT The present study was designed to investigate the antioxidant, antinociceptive and anti-inflammatory activities of the ethanol extract from Ageratum fastigiatum branches. Phytochemical screening and total phenol and flavonoid contents were determined. The antioxidant activity was assessed by 2,2-diphenyl-1-pycrilhydrazin (DPPH) and iron reducing power methods. The antinociceptive effect was evaluated using the acetic acid-induced writhing, formalin, hot plate and tail immersion assays; while the carrageenan-induced paw edema and pleurisy tests were performed to examine the anti-inflammatory activity against acute inflammation. The extract revealed the presence of flavonoids, tannins, coumarins, terpenes, sterols and saponins. Expressive levels of total phenols and flavonoids and a promising antioxidant effect were quantified. At the doses of 50, 100 and 200 mg/kg, the extract inhibited the writhing, reduced both phases of paw licking time and increased the reaction time on the hot plate. In the tail immersion test, the extract (50, 100 and 200 mg/kg) caused a significant inhibition of pain. In these doses, the paw edema, exudate volume and leucocyte mobilization were significantly reduced. These results suggest that A. fastigiatum can be an active source of substances with antioxidant, antinociceptive and anti-inflammatory activities, adding scientific support to the appropriate use in the Brazilian folk medicine.

scholarly journals Update on Eosinophilic Meningoencephalitis and Its Clinical Relevance

2009 ◽  
Vol 22 (2) ◽  
pp. 322-348 ◽  
Author(s):  
Carlos Graeff-Teixeira ◽  
Ana Cristina Arámburu da Silva ◽  
Kentaro Yoshimura
Keyword(s):  
Central Nervous System ◽  
Concomitant Administration ◽  
Definitive Diagnosis ◽  
Contaminated Water ◽  
Neoplastic Disease ◽  
Helminthic Infections ◽  
The Central Nervous System ◽  
New Compounds ◽  
Eosinophilic Meningoencephalitis ◽  
Etiologic Diagnosis

SUMMARY Eosinophilic meningoencephalitis is caused by a variety of helminthic infections. These worm-specific infections are named after the causative worm genera, the most common being angiostrongyliasis, gnathostomiasis, toxocariasis, cysticercosis, schistosomiasis, baylisascariasis, and paragonimiasis. Worm parasites enter an organism through ingestion of contaminated water or an intermediate host and can eventually affect the central nervous system (CNS). These infections are potentially serious events leading to sequelae or death, and diagnosis depends on currently limited molecular methods. Identification of parasites in fluids and tissues is rarely possible, while images and clinical examinations do not lead to a definitive diagnosis. Treatment usually requires the concomitant administration of corticoids and anthelminthic drugs, yet new compounds and their extensive and detailed clinical evaluation are much needed. Eosinophilia in fluids may be detected in other infectious and noninfectious conditions, such as neoplastic disease, drug use, and prosthesis reactions. Thus, distinctive identification of eosinophils in fluids is a necessary component in the etiologic diagnosis of CNS infections.

scholarly journals Analgesic Effects of Thiamine in Male Long Evans Rats

2017 ◽  
Vol 12 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Sayema Ainan ◽  
Noorzahan Begum ◽  
Taskina Ali
Keyword(s):  
Experimental Pain ◽  
Immersion Test ◽  
Writhing Test ◽  
Analgesic Effects ◽  
Inhibitory Mechanisms ◽  
Significant Decrement ◽  
Pain Models ◽  
Tail Immersion ◽  
Long Evans ◽  
Post Hoc

Background: The concept of analgesic effects of thiamine along with other B vitamins has been supported since long by various clinical and experimental evidences, though effects of individual thiamine on pain are yet to be clearly demonstrated.Objective: To assess the effects of increasing doses of thiamine supplementation on pain.Methods: Forty-eight (48) male Long Evans rats (200±20 gm) were given thiamine (100, 200, 250, mg/kg/day; experimental) or normal saline (5 ml/kg/day; control) intraperitonealy (i.p) for 7 consecutive days. The analgesic activity was evaluated by three experimental pain models, hot (52±0.50C) water tail immersion test, the interphase (6th-15th minutes) of formalin (50?l, 2.5%, subcutaneous) test and acetic acid (2%, i.p) induced writhing test. Statistical analysis was done by ANOVA followed by Bonferroni post hoc test and p?0.05 was considered as significant.Results: In tail immersion test, %MPE significantly increased after 200 (p?0.05) and 250 (p?0.001) mg/kg of thiamine. In the formalin test, thiamine significantly lowered the jerking frequency (p?0.05, p?0.001, p?0.001, respectively) and duration of flexing and licking (p?0.001, in all doses), compared to control. In addition, in writhing test, significant increment in latency of appearance of 1st writhe (p?0.001, in higher 2 doses) and significant decrement in frequency of writhes (p?0.01, p?0.001, p?0.001, respectively, in all doses) were observed.Conclusion: The results of this study conclude that, repetitive administration of thiamine may cause alleviation of pain through central as well as peripheral inhibitory mechanisms, which is dose dependent as well.Bangladesh Soc Physiol. 2017, June; 12(1): 1-9

scholarly journals Exploring Novel Molecular Targets for the Treatment of High-Grade Astrocytomas Using Peptide Therapeutics: An Overview

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 490 ◽  
Author(s):  
Giulia Guidotti ◽  
Liliana Brambilla ◽  
Daniela Rossi
Keyword(s):  
Malignant Gliomas ◽  
Genetic Alterations ◽  
Cellular Heterogeneity ◽  
High Grade ◽  
Therapeutic Approaches ◽  
Average Survival ◽  
The Central Nervous System ◽  
Specific Receptors ◽  
Models Of Disease ◽  
Pharmacologically Active

Diffuse astrocytomas are the most aggressive and lethal glial tumors of the central nervous system (CNS). Their high cellular heterogeneity and the presence of specific barriers, i.e., blood–brain barrier (BBB) and tumor barrier, make these cancers poorly responsive to all kinds of currently available therapies. Standard therapeutic approaches developed to prevent astrocytoma progression, such as chemotherapy and radiotherapy, do not improve the average survival of patients. However, the recent identification of key genetic alterations and molecular signatures specific for astrocytomas has allowed the advent of novel targeted therapies, potentially more efficient and characterized by fewer side effects. Among others, peptides have emerged as promising therapeutic agents, due to their numerous advantages when compared to standard chemotherapeutics. They can be employed as (i) pharmacologically active agents, which promote the reduction of tumor growth; or (ii) carriers, either to facilitate the translocation of drugs through brain, tumor, and cellular barriers, or to target tumor-specific receptors. Since several pathways are normally altered in malignant gliomas, better outcomes may result from combining multi-target strategies rather than targeting a single effector. In the last years, several preclinical studies with different types of peptides moved in this direction, providing promising results in murine models of disease and opening new perspectives for peptide applications in the treatment of high-grade brain tumors.

scholarly journals Gyejigachulbu-Tang Relieves Oxaliplatin-Induced Neuropathic Cold and Mechanical Hypersensitivity in Rats via the Suppression of Spinal Glial Activation

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Byung-Soo Ahn ◽  
Seong-Kyu Kim ◽  
Ha Neul Kim ◽  
Ji-Hye Lee ◽  
Ji-Hwan Lee ◽  
...  
Keyword(s):  
Cold Water ◽  
Immersion Test ◽  
Glial Activation ◽  
Mechanical Hypersensitivity ◽  
Spinal Dorsal ◽  
Cinnamomi Cortex ◽  
Tail Immersion ◽  
Paeoniae Radix ◽  
Pain Symptoms ◽  
Cold Hypersensitivity

Activation of spinal glial cells plays a crucial role in the pathogenesis of neuropathic pain. An administration of oxaliplatin, an important anticancer drug, often induces acute neuropathic cold hypersensitivity and/or mechanical hypersensitivity in patients. Gyejigachulbu-tang (GBT), a herbal formula comprisingCinnamomi Cortex, Paeoniae Radix, Atractylodis Lanceae Rhizoma, Zizyphi Fructus, Glycyrrhizae Radix, Zingiberis Rhizoma,andAconiti Tuber, has been used in East Asia to treat various pain symptoms, especially in cold patients. This study investigated whether and how GBT alleviates oxaliplatin-induced cold and mechanical hypersensitivity in rats. The behavioral signs of cold and mechanical hypersensitivity were evaluated by a tail immersion test in cold water (4°C) and a von Frey hair test, respectively. The significant cold and mechanical hypersensitivity were observed 3 days after an oxaliplatin injection (6 mg/kg, i.p.). Daily oral administration of GBT (200, 400, and 600 mg/kg) for 5 days markedly attenuated cold and mechanical hypersensitivity. Immunoreactivities of glial fibrillary acidic protein (GFAP, astrocyte marker) and OX-42 (microglia marker) in the spinal dorsal horn were significantly increased by an oxaliplatin injection, which were restored by GBT administration. These results indicate that GBT relieves oxaliplatin-induced cold and mechanical hypersensitivity in rats possibly through the suppression of spinal glial activation.

scholarly journals Analgesic and Antioxidant Activities of 4-Phenyl-1,5-benzodiazepin-2-one and Its Long Carbon Chains Derivatives

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Terence Nguema Ongone ◽  
Redouane Achour ◽  
Mostafa El Ghoul ◽  
Latyfa El Ouasif ◽  
Meryem El Jemli ◽  
...  
Keyword(s):  
Antioxidant Activity ◽  
Acetic Acid ◽  
Antioxidant Activities ◽  
Radical Scavenging ◽  
Reducing Power ◽  
Carbon Chain ◽  
Immersion Test ◽  
Tail Immersion ◽  
Reducing Power Assay

The aim of this work is to deepen the pharmacological effect of 4-phenyl-1,5-benzodiazepin-2-one derivatives which have a similar structure to nonionic surfactants: 4-phenyl-1,5-benzodiazepin-2-one is the hydrophilic head, and the carbon chain is hydrophobic tail. The antinociceptive activity of 4-phenyl-1,5-benzodiazepin-2-one derivatives was determined using acetic acid-induced writhing and tail immersion tests. In addition, the in vitro antioxidant activities of the tested derivatives were determined by using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging method and ferric reducing power assay. A single oral administration of these compounds at the doses of 50 and 100 mg/kg significantly reduced the number of abdominal writhes induced by acetic acid injection. Acute pretreatment with 4-phenyl-1,5-benzodiazepin-2-one derivatives at the dose of 100 mg/kg caused a significant increase in the tail withdrawal latency in the tail immersion test. Additionally, a significant scavenging activity in DPPH and reducing power was observed in testing antioxidant assays. Finally, we carried out a study of the antioxidant activity of these derivatives. The results of this study reveal that these compounds have a low antioxidant activity compared to the BHT. It decreases with the polarity of the molecule. The present study suggests that 4-phenyl-1,5-benzodiazepin-2-one derivatives possess potent antinociceptive and antioxidant effects, which suggest that the tested compounds may be useful in the treatment of pain and oxidation disorders.

Sign in / Sign up

Export Citation Format

Share Document