The Effect of Isoquinoline Alkaloids on Opiate Withdrawal

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Abstract:

Our interest has been centered on isoquinoline alkaloids obtained from Argemone mexicana (Papaveraceae), Aristolochia constricta (Aristolochiaceae) and the opium alkaloid, papaverine. In this respect, the effect of these isoquinoline alkaloids was investigated on contractions induced by naloxone of isolated guinea pig ileum acutely exposed to morphine in vitro. The activity of these alkaloids was compared to the control compound, papaverine. Furthermore, the effect of these isoquinoline alkaloids was also determined on naloxone-precipitated withdrawal in isolated guinea pig ileum exposed to DAMGO (highly selective mu opioid receptor agonist) and U50-488H (highly selective kappa opioid receptor agonist) to test whether the possible interaction of isoquinoline alkaloids on opioid withdrawal involves muand/ or kappa-opioid receptors. Isoquinoline alkaloids from A. mexicana (from 5x10-6 to 1x10-4 M), from A. constricta (1x10 -5-5x10 -5-1x10 -4 M) as well as papaverine treatment (1x10 -7-5x10 -6-1x10 -6 M) before or after the opioid agonists were able of both preventing and reversing the naloxone-induced contraction after exposure to mu(morphine and DAMGO) or kappa (U50-488H) opiate receptor agonists in a concentration-dependent manner. Both acetylcholine response and electrical stimulation were also reduced by isoquinoline alkaloids and papaverine treatment as well as the final opiate withdrawal was still reduced.

The results of the present study indicate that isoquinoline alkaloids as well as papaverine were able to produce significant influence on the opiate withdrawal in vitro and these compounds were able to exert their effects both at muand kappa opioid agonists.

Keywords: Argemone mexicana; Aristolochia constricta; Papaverine; guinea pig ileum; isoquinoline alkaloids; opiate withdrawal

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/092986706776055616

Affiliations: Dipartimento di Scienze Farmaceutiche, Universita di Salerno, Via Ponte Don Melillo, 84084, Italy.

Publication date: March 1, 2006

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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