Postischemic brain injury is affected stereospecifically by pentazocine in rats.
We tested whether rats treated with the sigma1-receptor ligand, (+)-pentazocine, during transient focal ischemia would have a smaller volume of postischemic brain infarction than rats treated with the nonspecific opioid-receptor ligand (-)-pentazocine. Rats underwent focal cerebral ischemia using the filament occlusion technique for 2 h, followed by 22 h of reperfusion. Rats received (+) or (-)-pentazocine (n = 9 each group) at a dose of 2 mg x kg(-1) x h(-1) by continuous intravenous infusion from 1 h of ischemia to 22 h of reperfusion. Triphenyltetrazolium-determined infarction volume of ipsilateral striatum ([+]-pentazocine, 19 +/- 4 mm3, mean +/- SEM; [-]-pentazocine, 44 +/- 5 mm3) and cerebral cortex ([+]-pentazocine, 26 +/- 12 mm3; [-]-pentazocine, 134 +/- 29 mm3) was smaller in rats treated with (+) compared with (-)-pentazocine. Infarction volume in rats treated with (-)-pentazocine was also very similar to the infarction volume in saline-treated control rats from our previous study (striatum 44 +/- 4 mm3; hemisphere 136 +/- 27 mm3). These data indicate that sigma1-receptors may play an important role in the mechanism of injury both in cortex and striatum after 2 h of transient focal ischemia in rat.
Takahashi
H
H
Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21287-4963, USA.
Traystman
R J
RJ
Hashimoto
K
K
London
E D
ED
Kirsch
J R
JR
D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology; D002544:Cerebral Infarction / Q000473:pathology / Q000517:prevention & control; D002560:Cerebrovascular Circulation; D004396:Coloring Agents; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology; D007262:Infusions, Intravenous; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000473:pathology; D008024:Ligands; D008297:Male; D008968:Molecular Conformation; D009292:Narcotic Antagonists; D009294:Narcotics / Q000008:administration & dosage / Q000819:agonists* / Q000737:chemistry / Q000627:therapeutic use; D010423:Pentazocine / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D051381:Rats; D011957:Receptors, Opioid / Q000187:drug effects; D017480:Receptors, sigma / Q000037:antagonists & inhibitors / Q000187:drug effects; D015424:Reperfusion; D012965:Sodium Chloride; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013778:Tetrazolium Salts
D000701:Analgesics, Opioid; D004396:Coloring Agents; D008024:Ligands; D009292:Narcotic Antagonists; D009294:Narcotics; D011957:Receptors, Opioid; D017480:Receptors, sigma; D013778:Tetrazolium Salts; D012965:Sodium Chloride; C009591:triphenyltetrazolium; D010423:Pentazocine