MedChemComm
December 1, 2011
Katherine M Prevatt-Smith, Kimberly M Lovell, Denise S Simpson et al.
50 citations
A modified compound, initially derived from a potent natural hallucinogen, surprisingly offers a new avenue for treating drug addiction. Scientists hypothesized that slight structural changes could enhance its therapeutic benefits. Through synthesizing and evaluating new versions, particularly focusing on their interaction with opioid receptors and impact on drug-seeking behaviors in rats, a specific analog was identified. This novel compound not only matched the original's potency at key brain receptors but also effectively reduced cocaine-induced drug-seeking. This discovery represents the first instance of such a modified compound demonstrating anti-addictive capabilities.
Bioorganic & medicinal chemistry
May 1, 2012
Kimberly M Lovell, Tamara Vasiljevik, Juan J Araya et al.
35 citations
A palladium-catalyzed cross-coupling reaction (Liebeskind-Srogl) applied to a modified natural product scaffold produces ketone analogs of salvinorin A at neutral pH and room temperature, expanding synthetic access to this class. A one-step microwave method converts salvinorin A to its 12-epimer, previously requiring multiple steps. Several new analogs (alkene 9 and aromatic compounds 12, 19, 23, 25, 26) retain affinity and selectivity for kappa opioid receptors (KOP), and the furan-2-yl analog (31) shows similar affinity to the parent compound. These results indicate that diverse aromatic groups attached to the decalin core may be tolerated by KOP receptors, potentially yielding additional ligands.
Topics in current chemistry
January 1, 2011
Kimberly M Lovell, Katherine M Prevatt-Smith, Anthony Lozama et al.
17 citations
Salvinorin A, a unique compound, stands out as the first opioid ligand discovered without a basic nitrogen, challenging traditional understanding. Researchers developed sophisticated synthetic methods to recreate and modify its complex structure, which features seven chiral centers. By focusing on specific structural changes, they successfully created new analogs. These efforts yielded promising compounds with diverse and interesting biological activities, highlighting the power of chemical synthesis in drug discovery.
European journal of pharmacology
November 15, 2013
Aashish S Morani, Amy Ewald, Katherine M Prevatt-Smith et al.
Activating the κ opioid receptor with the salvinorin A analogue 2-methoxy-methyl salvinorin B (MOM Sal B) at 0.3 mg/kg reduced cocaine-seeking behavior in rats, but also reduced sucrose reinforcement. No sedation was observed—locomotion in cocaine-induced hyperactivity and open field tests was unchanged—yet the forced swim test showed increased immobility and decreased swimming times, indicating pro-depressive effects. The compound thus modulates cocaine-seeking non-selectively without sedation, but depressive side effects may limit its therapeutic use.