Electrophysiological Study, Biodistribution in Mice, and Preliminary PET Evaluation in a Rhesus Monkey of 1-Amino-3-[18F]fluoromethyl-5-methyl-adamantane (18F-MEM): A Potential Radioligand for Mapping the NMDA-Receptor Complex

Stimulation of dopa decarboxylase activity in striatum of healthy human brain secondary to NMDA receptor antagonism with a low dose of amantadine

“…for several hours post-injection (Samnick et al, 1998); similar behaviour has been observed for [ 11 C]-Nmethylamantadine in pigs (P. Cumming and A. Gee, unpublished observations). Assuming a similar high distribution volume for amantadine, the plasma concentrations of amantadine measured in patients with advanced Parkinson's disease (4-24 µM; Verhagen Metman et al, 1998) suggest that steady-state concentrations of amantadine in living brain of those patients may have been 20-240 µM.…”

Effects of memantine, haloperidol, and cocaine on primary and conditioned reinforcement associated with cocaine in rhesus monkeys

“…That is, testing for effects on BS presentation occurred earlier during experimental sessions than it did for self-administration. A previous study, however, demonstrated that doses of memantine comparable to those used in the present study produced appreciable brain levels in the rhesus monkey within 5 min of intravenous injection and maintained these levels for up to 120 min (Samnick et al 1998). Alternatively, it may be the case that the determinants limiting peak rates of cocaine-maintained lever pressing under vehicle-control conditions (e.g., those nonspecific effects which may interfere with lever pressing) are attenuated by memantine although the efficacy of cocaine as a reinforcer (as reflected by decreases in BS presentation) is being reduced.…”

Radiolabeling of [18F]-fluoroethylnormemantine and initial in vivo evaluation of this innovative PET tracer for imaging the PCP sites of NMDA receptors

“…Chemical modification can modulate specificity and BBB crossing, and we could work on several derivatives, although it is important to preserve affinity for the receptor. The first memantine derivative tested ([ 18 F]-FMEM) had better BBB crossing (3.6% ID/g [19]) and similar affinity, but was rejected because of excessive interindividual variation and surprising kinetic behavior in white matter, as quantified by a two-tissue compartment model. The present memantine derivative seems to have a lower uptake in white matter, and could be a useful compound to carry on investigating in the memantine family.…”

“…There are many noncompetitive PCP site antagonists, and several potential radioligands have already been synthesized with several different radioisotopes ([ 11 C], [ 18 F], [ 123 I]) and recently reviewed [11][12][13]. First came MK-801 analogs [14], ketamine [15], phencyclidine or thienyl-phencyclidine analogues [16], and memantine [17][18][19], because they are well known antagonists of the intrachannel site of NMDAr. However, although many compounds were tested, for many of them, binding was too nonspecific, and brain retention was poor.…”

“…It has shown promising in vitro and in vivo binding in mice and monkeys [19], with good retention in the brain. However, investigations of this tracer's binding characteristics in humans have shown that its distribution does not reflect regional NMDAr concentration, owing to high nonspecific uptake in white matter [17].…”