Autoradiographic Distribution and Applied Pharmacological Characteristics of Dextromethorphan and Related Antitissue/Anticonvulsant Drugs and Novel Analogs.
Midterm rept. 27 Sep 93-26 Sep 94,
LONDON UNIV (UNITED KINGDOM) DEPT OF PHARMACOLOGY
Pagination or Media Count:
Dextromethorphan is an antitussive compound with anticonvulsant and neuroprotective properties arising from actions within the central nervous system of mammals. In the present study we have determined the distribution of 3H-dextromethorphan 3HJ-DM binding sites in normal rat brain and 72 hours after middle cerebral artery occlusion. The pattern of distribution did not correlate with that of the excitatory amino acid, N-methyl-D-aspartate NMDA, with which an association has previously been suggested on the basis of a weak pharmacological interaction. A decrease in binding within certain regions of the cerebral cortex of occluded animals was observed. However, this was limited and may be a consequence of the possible intracellular location of the DM sites or simply due to the period allowed between the occlusion and preparing the brain sections. At 72 hours 3H-DM binding was clearly not a marker for the degree of neuronal damage. At autoradiographic technique is also being developed for examining the binding of 3H-DM in post mortem human whole brain sections Whole coronal sections have been prepared and binding of 3H1-DM obtained. However, further developmental studies are required to obtain the optimal conditions for obtaining a distribution pattern of 3H-DM sites.