Properties of ibogaine and its principal metabolite (12-hydroxyibogamine) at the MK-801 binding site of the NMDA receptor complex

The putative anti-addiction alkaloid ibogaine and its principal metabolite 12-hydroxyibogamine appear to act at the (+)-5 methyl-10,11-dihydro-5 H-dibenzo[ a,d]cycloheten-5–10-imine maleate (MK-801) binding site in the N-methyl- d-aspartate (NMDA)-receptor cation channel. This conclusion is based on findings that both compounds competitively displaced specific [ 3H]MK-801 binding to membranes from postmortem human caudate and cerebellum and from frog spinal cord. Ibogaine was 4–6 fold more potent than its metabolite and both compounds were less potent (50–1000-fold) than MK-801 binding to the NMDA receptor. In addition, ibogaine (100 μM) and 12-hydroxyibogamine (1 mM) blocked (85–90% of control) the ability of NMDA (100μM, 5 s) to depolarize frog motoneurons in the isolated frog spinal cord. The prevention of NMDA-depolarizations in frog motoneurons showed use-dependency and was very similar to the block produced by MK-801. In view of the abilities of MK-801 to affect the responses to addictive substances in pre-clinical investigations, our results are compatible with the idea that the ability of ibogaine and 12-hydroxyibogamine to interrupt drug-seeking behavior may, in part, result from their actions at the MK-801 binding site

Assessment of Disability in Patients with Acute Traumatic Spinal Cord Injury: A Systematic Review of the Literature

Given the importance of accurately and reliably assessing disability in future clinical trials, which will test therapeutic strategies in acute spinal cord injury (SCI), we sought to appraise comprehensively studies that focused on the psychometric properties (i.e., reliability, validity, and responsiveness) of all previously used outcome measures in the SCI population. The search strategy included Medline, CINAHL, EMBASE, and Cochrane databases. Two reviewers independently assessed each study regarding eligibility, level of evidence (using Sackett's criteria), and quality. Of 363 abstracts captured in our search, 36 full articles fulfilled the inclusion and exclusion criteria. Eight different outcome measures were used to assess disability in the SCI population, including Functional Independence Measure (FIM), Spinal cord Injury Measure (SCIM), Walking Index for Spinal Cord Injury (WISCI), Quadriplegia Index of Function (QIF), Modified Barthel Index (MBI), Timed Up & Go (TUG), 6-min walk test (6MWT), and 10-m walk test (10MWT). While 19 of 36 studies provided level-4 evidence, the remaining 17 articles were classified as level-2b evidence. Most of the instruments showed convergent construct validity in the SCI population, but criterion validity was not examined due to the lack a gold standard for assessment of disability. All instruments were tested in the rehabilitation and/or community setting, but only FIM was examined in the acute care setting. Based on our results of quality assessment, the SCIM has the most appropriate performance regarding the instrument's psychometric properties. Nonetheless, further investigations are required to confirm the adequate performance of the SCIM as a comprehensive measure of functional recovery in patients with SCI in rehabilitative care. The expert panel of the Spinal Cord Injury Solutions Network (SCISN) that participated in the modified Delphi process endorsed these conclusions