PPBP [4-phenyl-1-(4-phenylbutyl) piperidine] decreases brain injury after transient focal ischemia in rats.

Abstract

BACKGROUND AND PURPOSE:

We tested the hypothesis that intravenous administration of the potent sigma-receptor ligand 4-phenyl-1-(4-phenylbutyl) piperidine (PPBP) during transient focal ischemia would decrease postischemic brain infarction volume in rats.

METHODS:

Rats underwent intravascular focal ischemia for 2 hours followed by 22 hours of reperfusion. Halothane anesthesia was used only during initiation and cessation of ischemia. Rats received saline (n = 10) or 1 mumol/kg per hour PPBP (n = 10) by continuous intravenous infusion starting 1 hour after the initiation of ischemia and continuing through 22 hours of reperfusion.

RESULTS:

There was no difference between groups in blood pressure, arterial blood gas values, and body temperature. Triphenyltetrazolium-determined infarction volume of ipsilateral cerebral cortex (saline, 39 +/- 6%; PPBP, 21 +/- 7% of ipsilateral hemisphere; mean +/- SEM) and striatum (saline, 68 +/- 6%; PPBP, 33 +/- 8% of ipsilateral striatum) was smaller in rats treated with PPBP than in rats treated with saline.

CONCLUSIONS:

These data indicate that sigma-receptors may play an important role in the mechanism of injury both in cortex and striatum after 2 hours of transient focal ischemia in rats. Because PPBP afforded protection when administered at the end of ischemia and during reperfusion, sigma-receptors may influence the progression of injury in ischemic border regions.

• Authors: H Takahashi, J R Kirsch, K Hashimoto, E D London, R C Koehler, R J Traystman
• Journal: Stroke (Stroke) Vol. 27 Issue 11 Pg. 2120-3 (Nov 1996) ISSN: 0039-2499 [Print] United States
• PMID: 8898825 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Neuroprotective Agents
• Receptors, sigma
• 4-phenyl-1-(4-phenylbutyl)piperidine
• Haloperidol

Topics

• Animals
• Cerebral Infarction (etiology, metabolism, pathology, prevention & control)
• Disease Models, Animal
• Haloperidol (administration & dosage, analogs & derivatives, therapeutic use)
• Infusions, Intravenous
• Ischemic Attack, Transient (complications, drug therapy, metabolism, pathology)
• Male
• Neuroprotective Agents (administration & dosage, therapeutic use)
• Rats
• Receptors, sigma (drug effects)
• Time Factors
• Treatment Outcome