Prodrugs of thyrotropin-releasing hormone and related peptides as central nervous system agents.
Prodrug design for brain delivery of small- and medium-sized neuropeptides was reviewed, focusing on thyrotropin-releasing hormone and structurally related peptides as examples. We have summarized our most important advances in methodology, as well as assessed the benefits and limitations of bioreversible chemical manipulation techniques to achieve targeting of the parent molecules into the central nervous system. The value of prodrug-amenable analogues as potential drug-like central nervous systems agents was highlighted.
Prokai-Tatrai
Katalin
K
Department of Pharmacology & Neuroscience, University of North Texas Health Science Center, Fort Worth, TX, USA. kprokai@hsc.unt.edu
Prokai
Laszlo
L
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000502:physiology*; D002490:Central Nervous System / Q000187:drug effects; D002491:Central Nervous System Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D000697:Central Nervous System Stimulants / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D004355:Drug Stability; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D011355:Prodrugs / Q000737:chemistry / Q000378:metabolism*; D013973:Thyrotropin-Releasing Hormone / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology
D002491:Central Nervous System Agents; D000697:Central Nervous System Stimulants; D010455:Peptides; D011355:Prodrugs; D013973:Thyrotropin-Releasing Hormone