The Synthesis and Analgesic Activities of Some Spiro[indan-l,3'-pyrrolidine] Derivatives Designed as Rigid Analogs of Profadol

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.

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Design, Synthesis and Pharmacological Evaluation of Novel Antiinflammatory and Analgesic O-Benzyloxime Compounds Derived From Natural Eugenol

Letters in Drug Design & Discovery ◽

10.2174/1570180815666180620145609 ◽

2019 ◽

Vol 16 (10) ◽

pp. 1157-1166

Author(s):

Rodrigo César da Silva ◽

Fabiano Veiga ◽

Fabiana Cardoso Vilela ◽

André Victor Pereira ◽

Thayssa Tavares da Silva Cunha ◽

...

Keyword(s):

Formalin Test ◽

Docking Studies ◽

Paw Edema ◽

Inhibitory Effects ◽

Structural Pattern ◽

Design Synthesis ◽

Drug Candidates ◽

Anti Inflammatory ◽

Analgesic Activities ◽

Cox 1

Background: : A new series of O-benzyloximes derived from eugenol was synthesized and was evaluated for its antinociceptive and anti-inflammatory properties. Methods: : The target compounds were obtained in good global 25-28% yields over 6 steps, which led us to identify compounds (Z)-5,6-dimethoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-one-O-(4- (methylthio)benzyloxime (8b), (Z)-5,6-dimethoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-one-O-4- bromobenzyloxime (8d) and (Z)-5,6-dimethoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-one-O-4- (methylsulfonyl)benzyloxime (8f) as promising bioactive prototypes. Results:: These compounds have significant analgesic and anti-inflammatory effects, as evidenced by formalin-induced mice paw edema and carrageenan-induced mice paw edema tests. In the formalin test, compounds 8b and 8f evidenced both anti-inflammatory and direct analgesic activities and in the carrageenan-induced paw edema, with compounds 8c, 8d, and 8f showing the best inhibitory effects, exceeding the standard drugs indomethacin and celecoxib. Conclusion: : Molecular docking studies have provided additional evidence that the pharmacological profile of these compounds may be related to inhibition of COX enzymes, with slight preference for COX-1. These results led us to identify the new O-benzyloxime ethers 8b, 8d and 8f as orally bioactive prototypes, with a novel structural pattern capable of being explored in further studies aiming at their optimization and development as drug candidates.

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The anti-inflammatory and analgesic activities of the ethyl acetate extract of Viburnum taitoense Hayata

Journal of Ethnopharmacology ◽

10.1016/j.jep.2020.113742 ◽

2021 ◽

Vol 269 ◽

pp. 113742

Author(s):

Xinduo Wu ◽

Jizhao Xie ◽

Li Qiu ◽

Luhui Zou ◽

Yunfeng Huang ◽

...

Keyword(s):

Ethyl Acetate ◽

Ethyl Acetate Extract ◽

Anti Inflammatory ◽

Analgesic Activities

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A comparison of the analgesic activities of 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP) and 6-chloro-2[1-piperazinyl]pyrazine (MK 212)

European Journal of Pharmacology ◽

10.1016/0014-2999(83)90235-2 ◽

1983 ◽

Vol 90 (2-3) ◽

pp. 179-184 ◽

Cited By ~ 14

Author(s):

Thomas F. Murray ◽

William McGill ◽

Darwin L. Cheney

Keyword(s):

Mk 212 ◽

Analgesic Activities

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Syntheses, Antiinflammatory, and Analgesic Activities of Arylbiurets

Archiv der Pharmazie ◽

10.1002/ardp.19903230607 ◽

1990 ◽

Vol 323 (6) ◽

pp. 355-359 ◽

Cited By ~ 5

Author(s):

Makoto Kajitani ◽

Tomio Yamazaki ◽

Shozo Yamada ◽

Motoaki Tanaka ◽

Kazuo Ogawa ◽

...

Keyword(s):

Analgesic Activities

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Semi-synthesis of Novel Buprenorphine Derivatives and their Anti-nociceptive Properties and Dependency Potential

Canadian Journal of Chemistry ◽

10.1139/cjc-2020-0429 ◽

2021 ◽

Author(s):

Zahra Hasanpour ◽

Peyman Salehi ◽

Lennart Bunch ◽

Mona Khoramjouy ◽

Morteza Bararjanian ◽

...

Keyword(s):

Opioid Receptors ◽

Analgesic Effect ◽

Preference Test ◽

Biological Properties ◽

Place Preference ◽

Tail Flick ◽

Tail Flick Test ◽

Active Compounds ◽

Methyl Group ◽

Analgesic Activities

Abstract: Novel 1,2,3-triazole-tethered N-norbuprenorphine derivatives with an OMe or OH group at the C3 position were synthesized alongside with evaluation of their analgesic properties. The analgesic activities of the resulting library were investigated via tail flick test in mice. Our results indicated that 10b and 10e were as effective as the starting compounds 8 and 9 with ED50 equal to 16.59 and 19.44 mg/kg, respectively. To investigate the effect of a methyl group at C3 on biological properties, the most active compounds were O-demethylated and their anti-nociceptive effects were assessed. The new O-demethylated derivatives (11b and 11e) showed better analgesic properties than the parent compounds with ED50 of 14.73 and 15.80 mg/kg, respectively. Naloxone prevented the analgesic effect of the synthesized compounds, indicating that the opioid receptors are highly involved in the anti-nociceptive effects of these. The potential dependency effects of the most potent derivatives were studied by condition place preference test in mice and compared to morphine and buprenorphine. Interestingly, 10b, 10e, 11b, and 11e did not show any dependency effect, similar to buprenorphine.

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Analgesic activities of the mixed opioid and NPFF receptors agonist DN-9 in a mouse model of formalin-induced orofacial inflammatory pain

Peptides ◽

10.1016/j.peptides.2018.10.010 ◽

2018 ◽

Vol 110 ◽

pp. 30-39

Author(s):

Ting Zhang ◽

Weidong Zhao ◽

Mengna Zhang ◽

Biao Xu ◽

Xuerui Shi ◽

...

Keyword(s):

Mouse Model ◽

Inflammatory Pain ◽

Analgesic Activities

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EVALUATION OF ANTIHYPERLIPIDEMIC, ANTI-INFLAMMATORY, AND ANALGESIC ACTIVITIES OF EURYCOMA LONGIFOLIA IN ANIMAL MODELS

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2017v9i3.16366 ◽

2017 ◽

Vol 9 (3) ◽

pp. 166

Author(s):

Phebe Hendra ◽

Fenty . ◽

Putu Ririn Andreani ◽

Bernadetha Maria Estika Pangestuti ◽

Jeffry Julianus

Keyword(s):

Acetic Acid ◽

Control Group ◽

Root Extract ◽

Paw Edema ◽

Edema Formation ◽

Eurycoma Longifolia ◽

Anti Inflammatory ◽

Analgesic Activities ◽

Enrich Diet ◽

Digital Caliper

Objective: To investigate the antihyperlipidemic, anti-inflammatory and analgesic properties of of E. longifolia root extract in animal models.Methods: In this study, glucose-fructose enriched diet-induced hyperlipidemia, carrageenan-induced paw edema and acetic acid-induced writhing were used to evaluate the anti-hypertriglyceridemia, anti-inflammatory and analgesic activities, respectively. At the end of the experiment of glucose-fructose enriched diet-induced hyperlipidemia, blood samples were collected and estimation of blood lipids were carried out. Edema thickness was measured using digital caliper at 0, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240, 270, 300, 330, and 360 min after carrageenan injection. The number of abdominal writhing for each mouse was observed and counted during a period of 1 h post injection of acetic acid.Results: E. longifolia root extract demonstrated a significant reduction of triglyceride levels (p<0.05) compared with the control group in glucose-fructose enrich diet in rats. In anti-inflammatory test, the extract significantly inhibited the carrageenan induced paw edema formation (p<0.05). The extract also significantly decreased the number of writhing in acetic acid-induced mice (p<0.05).Conclusion: E. longifolia root extract shown a significant anti-hypertriglyceridemia, anti-inflammatory and analgesic activities. Further studies are needed to determine mechanisms for its acitivities of E. longifolia root extract.

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