Therapeutic potential for adenosine receptor activation in ischemic brain injury.
The present report reviews the biochemical and physiological responses to adenosine receptor activation and how these responses underlie the ability of adenosine to couple energy demand with energy supply. In addition, activation of adenosine receptors pharmacologically is shown to initiate various reactions which could be responsible for the observed adenosine-mediated attenuation of the neuropathological consequences of brain ischemia. Also reported is the extent to which side effects such as hypothermia can contribute to the observed efficacy of adenosine agonist administration in the small animal model of ischemia. Data from various in vitro and in vivo ischemia studies is presented showing that neuroprotection can be achieved following pharmacological activation of adenosine receptors either through agonists with high affinity for A1 adenosine receptors or drugs which potentiate endogenous adenosine levels. In general the data support utilization of adenosine receptor activation as a means of attenuating ischemic brain damage.
Miller
L P
LP
Gensia Pharmaceuticals, Inc., San Diego, CA 92121.
Hsu
C
C
D000241:Adenosine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use*; D000818:Animals; D001921:Brain / Q000502:physiology / Q000503:physiopathology; D001930:Brain Injuries / Q000188:drug therapy* / Q000503:physiopathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D008959:Models, Neurological; D011983:Receptors, Purinergic / Q000187:drug effects / Q000502:physiology*
D011983:Receptors, Purinergic; D000241:Adenosine