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 preclini cal screening for potential neurotoxicologic side effects before intro ducing new therapeutic drugs for intrathecal (IT) administration. This study was undertaken to determine whether two drugs with possible ant inociceptive effects, the N-methyl-D-aspartate receptor antagonist 3-( 2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) and the adenosi ne agonist R-phenylisopropyladenosine (R-PIA), would affect SCBF after IT administration in the rat. SCBF was measured 30 min after IT injec tion of either saline, 4 nmol of CPP or 10 nmol of R-PIA in anesthetiz ed rats by quantitative autoradiography with [C-14]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 matt er 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 provocati ve doses within the upper pharmacologic dose range, reduces SCBF in ra ts 30 min after IT injection. This indicates that neither neurotoxicol ogic nor antinociceptive effects are likely to occur due to decrease i n SCBE Our results do not indicate that these drugs should be avoided for the treatment of pain.