Tissue distribution of two NMDA receptor antagonists, [3H]CGS 19755 and [3H]MK-801, after intrathecal injection in mice.
The tissue distribution of [3H]cis-4-phosphonomethyl-2-piperidine carboxylic acid (CGS 19755) and [3H](+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imi ne (NK-801) was investigated after a single IT injection into lumbar spinal cord of mice. The level of radioactivity was analyzed in the lumbar, thoracic, and cervical spinal cord, brainstem, frontal cortex, liver, lungs, kidneys, stomach, intestine, spleen, heart, and blood from 5 min up to 6 h after injection. Within the CNS, [3H]CGS 19755 redistributed slowly from the site of injection toward the brainstem and cortex, peaking in the cortex 3-4 h after IT injection. At no time, however, did the relative level per gram of tissue in the frontal cortex exceed 10% of the relative level in the lumbar region of the spinal cord. The highest peripheral level of [3H]CGS 19755 was found in the kidneys. [3H]MK-801 redistributed rapidly from the spinal cord injection site to the peripheral organs. The highest peripheral levels of [3H]MK-801 were found in the lungs and liver, where the radioactivity peaked at 10 and 30-60 min, respectively, after injection. The relative levels of [3H]CGS 19755 were consistently higher in CNS tissues (except for the first 15 min in the frontal cortex) and blood than the corresponding levels of [3H]MK-801. The opposite relationship was true in the liver, lungs, kidneys, stomach, intestine, spleen, and heart. The effect on the response latency in the hot-plate test was quantified in the same animals immediately prior to sacrifice for the distribution study.(ABSTRACT TRUNCATED AT 250 WORDS)
Näsström
J
J
Astra Pain Control, Preclinical Research, Södertälje, Sweden.
Böö
E
E
Ståhlberg
M
M
Berge
O G
OG
D000818:Animals; D016291:Dizocilpine Maleate / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors*; D010147:Pain Measurement / Q000187:drug effects; D010875:Pipecolic Acids / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D011930:Reaction Time / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D014018:Tissue Distribution
D010875:Pipecolic Acids; D016194:Receptors, N-Methyl-D-Aspartate; C053672:selfotel; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate