Novel neuroprotective tripeptides and dipeptides.
It has long been recognized that thyrotropin-releasing hormone (TRH) and certain TRH analogues are neuroprotective in a variety of animal models of CNS trauma. In addition to these neuroprotective actions, TRH and most TRH analogues have other physiological actions that may not be desirable for treatment of acute injury, such as analeptic, autonomic, and endocrine effects. We have developed a series of dual-substituted TRH analogues that have strong neuroprotective actions, but are largely devoid of these other physiological actions. In addition, we have developed a family of cyclized dipeptides (diketopiperazines), structurally somewhat related to a metabolic product of TRH, that appear even more effective as neuroprotective agents in vitro and in vivo, and may have nootropic properties. Here, we review these novel tripeptide and dipeptide compounds.
Faden
Alan I
AI
Department of Neuroscience, Georgetown University Medical Center, 3970 Reservoir Road NW, Research Building, Room EP04, Washington, District of Columbia 20057, USA. fadena@georgetown.edu
Knoblach
Susan M
SM
Movsesyan
Vilen A
VA
Lea
Paul M
PM
Cernak
Ibolja
I
D000818:Animals; D003500:Cyclization; D006801:Humans; D018696:Neuroprotective Agents; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives
D018696:Neuroprotective Agents; D009842:Oligopeptides; D013973:Thyrotropin-Releasing Hormone