The pharmacology of ryanodine and related compounds.
The goal of this review has been to describe the current state of the pharmacology of ryanodine and related compounds relative to the vertebrate RyRs. Resolution of questions concerning the molecular properties of RyR channel function and the contributions made by the RyR isoforms to cellular signaling in a variety of tissues will require the production of new pharmacological agents directed against these proteins. Novel naturally occurring ryanodine congeners have been identified, and significant advances have been made in developing chemical approaches that permit the structure of ryanodine to be derivatized in selective ways. Moreover, several of these changes have yielded compounds that differ in their binding affinities and in their abilities to modify the properties of the RyR channels. These advances give substance to the possibility of designing the required pharmacological agents based on rational design changes of the structure ryanodine.
Sutko
J L
JL
Department of Pharmacology, University of Nevada School of Medicine, Reno 89557, USA.
Airey
J A
JA
Welch
W
W
Ruest
L
L
D000215:Acylation; D000478:Alkylation; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism*; D002148:Calmodulin-Binding Proteins / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D009124:Muscle Proteins / Q000187:drug effects* / Q000378:metabolism; D012433:Ryanodine / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D019837:Ryanodine Receptor Calcium Release Channel; D013329:Structure-Activity Relationship; D014714:Vertebrates; D015262:Xenobiotics / Q000009:adverse effects* / Q000494:pharmacology / Q000633:toxicity
D015220:Calcium Channels; D002148:Calmodulin-Binding Proteins; D009124:Muscle Proteins; D019837:Ryanodine Receptor Calcium Release Channel; D015262:Xenobiotics; D012433:Ryanodine; D002118:Calcium