Synthesis of Biased Dopamine Agonists for In Vivo Testing
Start Date
April 2025
Location
2nd floor - Library
Abstract
Dopamine is a neurotransmitter that plays a role in various brain functions, including the regulation of behavior and cognition, voluntary movement, motivation, sleep, mood, attention, working memory, and learning. Dopamine receptors are expressed throughout the entire body, functioning both in the central and peripheral nervous system. Many drugs target dopamine receptors, with a variety of implications due to the binding and actions of these drugs. Dopamine agonists are drugs that bind to dopamine receptors and stimulate a response. Dopamine receptors are G protein-coupled receptors (GPCRs), meaning when a ligand binds to the receptor, intracellular signaling pathways are initiated. Two possible pathways that can be initiated are cyclic AMP (cAMP) accumulation and β-arrestin pathways. Agonists can be biased towards one pathway over another, meaning they will preferentially bind to a certain receptor, leading to a particular signaling pathway. Two biased dopamine agonists, N-Benzyl-2-(3-(4-(2,3-dichlorophenyl)piperazin-1-yl)propyl)-1-methyl-4-phenyl-1H-imidazole-5-carboxamide (cAMP biased) and 5-(3-(4-(2,3-Dichlorophenyl)piperazi-1-yl)propoxy)benzo[d]thiazole (β-arrestin biased), will be synthesized, then tested for bias in vivo, particularly in C. elegans. Based upon the ratio between the pathways, the bias of the agonist can be confirmed and an exact ratio determined.
Synthesis of Biased Dopamine Agonists for In Vivo Testing
2nd floor - Library
Dopamine is a neurotransmitter that plays a role in various brain functions, including the regulation of behavior and cognition, voluntary movement, motivation, sleep, mood, attention, working memory, and learning. Dopamine receptors are expressed throughout the entire body, functioning both in the central and peripheral nervous system. Many drugs target dopamine receptors, with a variety of implications due to the binding and actions of these drugs. Dopamine agonists are drugs that bind to dopamine receptors and stimulate a response. Dopamine receptors are G protein-coupled receptors (GPCRs), meaning when a ligand binds to the receptor, intracellular signaling pathways are initiated. Two possible pathways that can be initiated are cyclic AMP (cAMP) accumulation and β-arrestin pathways. Agonists can be biased towards one pathway over another, meaning they will preferentially bind to a certain receptor, leading to a particular signaling pathway. Two biased dopamine agonists, N-Benzyl-2-(3-(4-(2,3-dichlorophenyl)piperazin-1-yl)propyl)-1-methyl-4-phenyl-1H-imidazole-5-carboxamide (cAMP biased) and 5-(3-(4-(2,3-Dichlorophenyl)piperazi-1-yl)propoxy)benzo[d]thiazole (β-arrestin biased), will be synthesized, then tested for bias in vivo, particularly in C. elegans. Based upon the ratio between the pathways, the bias of the agonist can be confirmed and an exact ratio determined.
