{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T16:17:32Z","timestamp":1792167452473,"version":"4.4.0"},"reference-count":116,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T00:00:00Z","timestamp":1736899200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Vicerrectorado de Investigaci\u00f3n of the Universidad Cat\u00f3lica de Santa Mar\u00eda","award":["27038-R-2019"],"award-info":[{"award-number":["27038-R-2019"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Epilepsy is a chronic neurological disorder that affects nearly 50 million people worldwide. Experimental evidence suggests that epileptic neurons are linked to the endocannabinoid system and that inhibition of the FAAH enzyme could have neuroprotective effects by increasing the levels of endogenous endocannabinoid anandamide. In this context, the use of macamides as therapeutic agents in neurological diseases has increased in recent years. With a similar structure to anandamide, several theories point to the FAAH\u2013macamide interaction as a possible cause of FAAH enzymatic inhibition. In this work, we used in silico and in vivo techniques to analyze the potential therapeutic effect of three synthetic macamides in the treatment of epilepsy: N-3-methoxybenzyl-oleamide (3-MBO), N-3-methoxybenzyl-linoleamide (3-MBL), and N-3-methoxybenzyl-linolenamide (3-MBN). In the first stage, an in silico analysis was conducted to explore the energetic affinity of these macamides with rFAAH and their potential inhibitory effect. MD simulations, molecular docking, and MM\/PBSA calculations were used for these purposes. Based on our results, we selected the two best macamides and performed an in vivo study to analyze their therapeutic effect in male Sprague Dawley rat models. Rats were subjected to an in vivo induction of epileptic status by the intraperitoneal injection of pilocarpine and analyzed according to the Racine scale. In silico results showed an energetic affinity of three macamides and a possible \u201cplugging\u201d effect of the membrane access channel to the active site as a potential cause of FAAH inhibition. On the other hand, the in vivo results showed an anticonvulsant effect of both macamides, with 3-MBL being the most active, resulting in a higher survival probability in the rats. This work represents one of the first studies on the use of macamides for the treatment of epilepsy.<\/jats:p>","DOI":"10.3390\/molecules30020333","type":"journal-article","created":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T04:55:19Z","timestamp":1737003319000},"page":"333","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Anticonvulsant Effects of Synthetic N-(3-Methoxybenzyl)oleamide and N-(3-Methoxybenzyl)linoleamide Macamides: An In Silico and In Vivo Study"],"prefix":"10.3390","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7908-8230","authenticated-orcid":false,"given":"Karin Jannet","family":"Vera-L\u00f3pez","sequence":"first","affiliation":[{"name":"Escuela Profesional de Farmac\u00eda y Bioqu\u00edmica, Universidad Cat\u00f3lica de Santa Mar\u00eda, Urb. San Jos\u00e9 s\/n, Umacollo, Arequipa 04000, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2921-5681","authenticated-orcid":false,"given":"Jorge Alberto","family":"Aguilar-Pineda","sequence":"additional","affiliation":[{"name":"Instituto de F\u00edsica \u201cLuis Rivera Terrazas\u201d, Benem\u00e9rita Universidad Aut\u00f3noma de Puebla, Av. San Claudio, Cd. Universitaria, Apdo. Postal J-48, Puebla 72570, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0915-2358","authenticated-orcid":false,"given":"Rodrigo Mart\u00edn","family":"Moscoso-Palacios","sequence":"additional","affiliation":[{"name":"Escuela Profesional de Farmac\u00eda y Bioqu\u00edmica, Universidad Cat\u00f3lica de Santa Mar\u00eda, Urb. San Jos\u00e9 s\/n, Umacollo, Arequipa 04000, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7842-9286","authenticated-orcid":false,"given":"Gonzalo","family":"Davila-Del-Carpio","sequence":"additional","affiliation":[{"name":"Escuela Profesional de Farmac\u00eda y Bioqu\u00edmica, Universidad Cat\u00f3lica de Santa Mar\u00eda, Urb. San Jos\u00e9 s\/n, Umacollo, Arequipa 04000, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0976-3349","authenticated-orcid":false,"given":"Jos\u00e9 Luis","family":"Manrique-Murillo","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n en Ingenier\u00eda Molecular\u2014CIIM, Universidad Cat\u00f3lica de Santa Mar\u00eda, Urb. San Jos\u00e9 s\/n\u2014Umacollo, Arequipa 04000, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6539-1207","authenticated-orcid":false,"given":"Badhin","family":"G\u00f3mez","sequence":"additional","affiliation":[{"name":"Escuela Profesional de Farmac\u00eda y Bioqu\u00edmica, Universidad Cat\u00f3lica de Santa Mar\u00eda, Urb. San Jos\u00e9 s\/n, Umacollo, Arequipa 04000, Peru"},{"name":"Centro de Investigaci\u00f3n en Ingenier\u00eda Molecular\u2014CIIM, Universidad Cat\u00f3lica de Santa Mar\u00eda, Urb. San Jos\u00e9 s\/n\u2014Umacollo, Arequipa 04000, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8975-3740","authenticated-orcid":false,"given":"Minerva","family":"Gonz\u00e1lez-Melchor","sequence":"additional","affiliation":[{"name":"Instituto de F\u00edsica \u201cLuis Rivera Terrazas\u201d, Benem\u00e9rita Universidad Aut\u00f3noma de Puebla, Av. San Claudio, Cd. Universitaria, Apdo. Postal J-48, Puebla 72570, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5671-4593","authenticated-orcid":false,"given":"Rita","family":"Nieto-Montesinos","sequence":"additional","affiliation":[{"name":"Escuela Profesional de Farmac\u00eda y Bioqu\u00edmica, Universidad Cat\u00f3lica de Santa Mar\u00eda, Urb. San Jos\u00e9 s\/n, Umacollo, Arequipa 04000, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"161","DOI":"10.21273\/HORTSCI.38.2.161","article-title":"Andean root and tuber crops: Underground rainbows","volume":"38","author":"Flores","year":"2003","journal-title":"HortScience"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1770","DOI":"10.1007\/s12035-018-1115-8","article-title":"Inhibition of fatty acid amide hydrolase (FAAH) by macamides","volume":"56","author":"Alasmari","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"4550","DOI":"10.1080\/14786419.2019.1698572","article-title":"Lepidium meyenii (Maca) in male reproduction","volume":"35","author":"Tafuri","year":"2021","journal-title":"Nat. Prod. 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