The pyrrolidine ring and its relation with the psychoactivity of mitragynine

Mitragynine, the major alkaloid of Mitragyna speciosa has been widely studied for its anti-addictive properties. Similar to morphine, mitragynine mainly acts at mu-opioid receptor which is the main target to treat opioid dependency. Unfortunately, it is believed that the psychoactivity of mitragynin...

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Main Authors:	Mohd Ghazali, Masitah, Ridzwan, Irna Elina, Suhaimi, Maryam Saadah, Kasmuri, Abdul Razak, Hashim, Ridzwan, Aziz, Mohd Razif, Syd Mohmad Faudzi, Syed Mohd Syahmi
Format:	Conference or Workshop Item
Language:	English
Published:	2015
Subjects:	QD Chemistry RS Pharmacy and materia medica
Online Access:	http://irep.iium.edu.my/44308/ http://irep.iium.edu.my/44308/1/44308.pdf

id	iium-44308
recordtype	eprints
spelling	iium-443082015-10-05T05:46:36Z http://irep.iium.edu.my/44308/ The pyrrolidine ring and its relation with the psychoactivity of mitragynine Mohd Ghazali, Masitah Ridzwan, Irna Elina Suhaimi, Maryam Saadah Kasmuri, Abdul Razak Hashim, Ridzwan Aziz, Mohd Razif Syd Mohmad Faudzi, Syed Mohd Syahmi QD Chemistry RS Pharmacy and materia medica Mitragynine, the major alkaloid of Mitragyna speciosa has been widely studied for its anti-addictive properties. Similar to morphine, mitragynine mainly acts at mu-opioid receptor which is the main target to treat opioid dependency. Unfortunately, it is believed that the psychoactivity of mitragynine is limiting its use. Compared to morphine, mitragynine contains pyrrolidine ring in its chemical structure, which is suspected as the contributor to the unwanted psychoactive activities seen. Therefore, the aim of this study is to investigate the relationship between pyrrolidine ring and mitragynine’s psychoactive effects. This was done by synthesizing an analogue of mitragynine with epoxy ring to replace pyrrolidine. A tail-flick test (52°C) was conducted in vivo using ICR mice in order to establish the basal analgesic effect for mitragynine mediated by the mu-opioid receptor, with morphine as standard reference. 80 mg of mitragynine was found to be equipotent to 10 mg of morphine (n = 6, P < 0.001). The analogue of mitragynine (that has epoxy ring instead of pyrrolidine ring) was generated by total synthesis using 2-benzofuran-3-yl-ethylamine as the starting material involved three major reaction steps. Each intermediates and reaction products were purified using column chromatography. The analogue has been confirmed using 1H-NMR, 13-C NMR and Mass Spectra. This analogue was then evaluated using the tail-flick test to identify the activity of any mu-opioid receptor of the new analogue. The psychoactivity of this new analogue is currently under evaluation in vivo using an open-field test in ICR mice to observe any behavioural activity related to psychoactive effects. The intensity will be compared to mitragynine. 2015-03-22 Conference or Workshop Item NonPeerReviewed application/pdf en http://irep.iium.edu.my/44308/1/44308.pdf Mohd Ghazali, Masitah and Ridzwan, Irna Elina and Suhaimi, Maryam Saadah and Kasmuri, Abdul Razak and Hashim, Ridzwan and Aziz, Mohd Razif and Syd Mohmad Faudzi, Syed Mohd Syahmi (2015) The pyrrolidine ring and its relation with the psychoactivity of mitragynine. In: International Conference on Natural Products 2015 (ICNP 2015), 24-25 March 2015, Double Tree by Hilton, Johor Bahru.
repository_type	Digital Repository
institution_category	Local University
institution	International Islamic University Malaysia
building	IIUM Repository
collection	Online Access
language	English
topic	QD Chemistry RS Pharmacy and materia medica
spellingShingle	QD Chemistry RS Pharmacy and materia medica Mohd Ghazali, Masitah Ridzwan, Irna Elina Suhaimi, Maryam Saadah Kasmuri, Abdul Razak Hashim, Ridzwan Aziz, Mohd Razif Syd Mohmad Faudzi, Syed Mohd Syahmi The pyrrolidine ring and its relation with the psychoactivity of mitragynine
description	Mitragynine, the major alkaloid of Mitragyna speciosa has been widely studied for its anti-addictive properties. Similar to morphine, mitragynine mainly acts at mu-opioid receptor which is the main target to treat opioid dependency. Unfortunately, it is believed that the psychoactivity of mitragynine is limiting its use. Compared to morphine, mitragynine contains pyrrolidine ring in its chemical structure, which is suspected as the contributor to the unwanted psychoactive activities seen. Therefore, the aim of this study is to investigate the relationship between pyrrolidine ring and mitragynine’s psychoactive effects. This was done by synthesizing an analogue of mitragynine with epoxy ring to replace pyrrolidine. A tail-flick test (52°C) was conducted in vivo using ICR mice in order to establish the basal analgesic effect for mitragynine mediated by the mu-opioid receptor, with morphine as standard reference. 80 mg of mitragynine was found to be equipotent to 10 mg of morphine (n = 6, P < 0.001). The analogue of mitragynine (that has epoxy ring instead of pyrrolidine ring) was generated by total synthesis using 2-benzofuran-3-yl-ethylamine as the starting material involved three major reaction steps. Each intermediates and reaction products were purified using column chromatography. The analogue has been confirmed using 1H-NMR, 13-C NMR and Mass Spectra. This analogue was then evaluated using the tail-flick test to identify the activity of any mu-opioid receptor of the new analogue. The psychoactivity of this new analogue is currently under evaluation in vivo using an open-field test in ICR mice to observe any behavioural activity related to psychoactive effects. The intensity will be compared to mitragynine.
format	Conference or Workshop Item
author	Mohd Ghazali, Masitah Ridzwan, Irna Elina Suhaimi, Maryam Saadah Kasmuri, Abdul Razak Hashim, Ridzwan Aziz, Mohd Razif Syd Mohmad Faudzi, Syed Mohd Syahmi
author_facet	Mohd Ghazali, Masitah Ridzwan, Irna Elina Suhaimi, Maryam Saadah Kasmuri, Abdul Razak Hashim, Ridzwan Aziz, Mohd Razif Syd Mohmad Faudzi, Syed Mohd Syahmi
author_sort	Mohd Ghazali, Masitah
title	The pyrrolidine ring and its relation with the psychoactivity of mitragynine
title_short	The pyrrolidine ring and its relation with the psychoactivity of mitragynine
title_full	The pyrrolidine ring and its relation with the psychoactivity of mitragynine
title_fullStr	The pyrrolidine ring and its relation with the psychoactivity of mitragynine
title_full_unstemmed	The pyrrolidine ring and its relation with the psychoactivity of mitragynine
title_sort	pyrrolidine ring and its relation with the psychoactivity of mitragynine
publishDate	2015
url	http://irep.iium.edu.my/44308/ http://irep.iium.edu.my/44308/1/44308.pdf
first_indexed	2023-09-18T21:03:00Z
last_indexed	2023-09-18T21:03:00Z
_version_	1777410748897558528

The pyrrolidine ring and its relation with the psychoactivity of mitragynine

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