Ropanicant (SUVN-911), an α4β2 nicotinic acetylcholine receptor antagonist intended for the treatment of depressive disorders: pharmacological, behavioral, and neurochemical characterization.
Rationale: Ropanicant (SUVN-911) (3-(6-Chloropyridine-3-yloxymethyl)-2-azabicyclo (3.1.0) hexane hydrochloride) is a novel α4β2 nicotinic acetylcholine receptor (nAChR) antagonist being developed for the treatment of depressive disorders. Objectives: Pharmacological and neurochemical characterizatio...
| Publicado en: | Psychopharmacology Vol. 239; no. 7; pp. 2215 - 2233 |
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| Autores principales: | , , , , , , , , , , , , , , , |
| Formato: | Journal Article |
| Publicado: |
Springer Nature
Jul2022
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=157528532&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 157528532 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00333158 EJD jtl: Psychopharmacology issn: 00333158 maglogo: N pubinfo: dt: Jul2022 vid: 239 iid: 7 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 157528532 155798504 10.1007/s00213-022-06108-6 157528532 ppf: 2215 ppct: 18 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Ropanicant (SUVN-911), an α4β2 nicotinic acetylcholine receptor antagonist intended for the treatment of depressive disorders: pharmacological, behavioral, and neurochemical characterization. aug: au: Nirogi, Ramakrishna Abraham, Renny Jayarajan, Pradeep Goura, Venkatesh Kallepalli, Rajesh Medapati, Rajesh babu Tadiparthi, Jayaprakash Goyal, Vinod kumar Pandey, Santosh kumar Subramanian, Ramkumar Petlu, Surendra Thentu, Jagadeesh Babu Palacharla, Veera Raghava Chowdary Gagginapally, Shankar Reddy Mohammed, Abdul Rasheed Jasti, Venkat affil: Suven Life Sciences Ltd, 500034, Hyderabad, India sug: ab: Rationale: Ropanicant (SUVN-911) (3-(6-Chloropyridine-3-yloxymethyl)-2-azabicyclo (3.1.0) hexane hydrochloride) is a novel α4β2 nicotinic acetylcholine receptor (nAChR) antagonist being developed for the treatment of depressive disorders. Objectives: Pharmacological and neurochemical characterization of Ropanicant to support a potential molecule for the treatment of depressive disorders. Methods: Ropanicant was assessed for antidepressant-like activity using the rat forced swimming test (FST) and differential reinforcement of low rate −72 s (DRL-72 s). Alleviation of anhedonia was assessed in chronic mild stress model using sucrose preference test. To understand the mechanism of action, serotonin levels, ionized calcium-binding adaptor molecule 1 (Iba1), and brain-derived neurotrophic factor (BDNF) were determined. The onset of antidepressant-like activity was determined using the reduction in submissive behavior assay. The effects on cognition and sexual functions were assessed using the object recognition task and sexual dysfunction assay respectively. Interaction of Ropanicant, TC-5214, and methyllycaconitine (MLA) with citalopram was investigated individually in mice FST. Results: Ropanicant exhibited antidepressant like properties in the FST and DRL-72 s. A significant reduction in anhedonia was observed in the sucrose preference test. Oral administration of Ropanicant produced a significant increase in serotonin and BDNF levels, with a reduction in the Iba1 activity. The onset of antidepressant like effect with Ropanicant was within a week of treatment, and was devoid of cognitive dulling and sexual dysfunction. While Ropanicant potentiated the effect of citalopram in FST, such an effect was not observed with MLA or TC-5214. Conclusions: Preclinical studies with Ropanicant support the likelihood of its therapeutic utility in the treatment of depressive disorders. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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