Spinal cord blood flow after intrathecal injection of a N-methyl-D-aspartate receptor antagonist or an adenosine receptor agonist in rats.
Evaluation of spinal cord blood flow (SCBF) is important as a preclinical screening for potential neurotoxicologic side effects before introducing new therapeutic drugs for intrathecal (IT) administration. This study was undertaken to determine whether two drugs with possible antinociceptive effects, the N-methyl-D-aspartate receptor antagonist 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) and the adenosine agonist R-phenylisopropyladenosine (R-PIA), would affect SCBF after IT administration in the rat. SCBF was measured 30 min after IT injection of either saline, 4 nmol of CPP or 10 nmol or R-PIA in anesthetized rats by quantitative autoradiography with [14C]iodantipyrine as a tracer. No differences in SCBF were found between groups treated with saline or CPP. In the group where R-PIA was administered IT, grey matter blood flow was 10% greater than in the group that received saline, whereas no differences were found in white matter blood flow or in the grey/white matter ratio between the groups. We concluded that neither CPP nor R-PIA, when administered IT to anesthetized rats in provocative doses within the upper pharmacologic dose range, reduces SCBF in rats 30 min after IT injection. This indicates that neither neurotoxicologic nor antinociceptive effects are likely to occur due to decrease in SCBF. Our results do not indicate that these drugs should be avoided for the treatment of pain.
Kristensen
J D
JD
Department of Anesthesiology, University Hospital, Uppsala, Sweden.
Karlsten
R
R
Gordh
T
T
Holtz
A
A
D000818:Animals; D007278:Injections, Spinal; D008297:Male; D010660:Phenylisopropyladenosine / Q000008:administration & dosage*; D010879:Piperazines / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012039:Regional Blood Flow / Q000187:drug effects; D013116:Spinal Cord / Q000098:blood supply*
D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; D010660:Phenylisopropyladenosine; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid