Disease relevance of Selfotel

• Termination of Acute Stroke Studies Involving Selfotel Treatment. ASSIST Steering Committed [1].
• Both the visceral hyperalgesia and the decrease in somatic pain thresholds were prevented by prior intrathecal CGS-19755 or NBQX injections [2].
• Furthermore, CGS-19755, 10 mg/kg intraperitoneally, begun either before or after ischemia substantially reduced calcium influx into ischemic neurons as evidenced by reduced calcium-calmodulin binding [3].
• We conclude that CGS-19755 prevents calcium entry into ischemic neurons and may be effective therapy for very acute cerebral ischemia [3].
• When CGS-19755 was combined with mild hypothermia the effects of repetitive ischemia were completely abolished in all but one gerbil [4].

Psychiatry related information on Selfotel

• In contrast, mice that had received the repeated treatment regimen of CGS 19755 increased motor activity in response to challenge doses of 30 and 54 mg/kg [5].
• CGS 19755 inhibited convulsions elicited by maximal electroshock in rat (ED50 = 3.8 mg/kg i.p. 1 hr after administration) and in mouse (ED50 = 2.0 mg/kg i.p. 0.5 hr after administration) [6].
• MK-801 (0.01-0.03 mg/kg, i.v.) and CGS-19755 (1-10 mg/kg, i.v.) significantly augmented scopolamine-induced deficit in the non-delayed maze task and impaired the short-term memory in the 5-min delay-interposed task [7].
• CGS 19755 (3.0 mg/kg) attenuated performance, decreased nose-pokes (an activity necessary to trigger the presentation of the discriminative stimulus and the presentation of the response levers), and increased response latencies (time from 'opportunity to leverpress' to 'actual leverpress') [8].

High impact information on Selfotel

• NMDA receptor antagonist (CGS-19755, 20 nmol) or AMPA/kainate receptor antagonist (NBQX, 20 nmol) was injected intrathecally before low-pH injections [2].
• The in vivo neuroprotective effect and brain levels of cis-4-phosphonomethyl-2-piperidine carboxylic acid (CGS 19755), a competitive N-methyl-D-aspartate (NMDA) antagonist, were compared with its in vitro neuroprotective effects [9].
• BACKGROUND AND PURPOSE: CGS 19755 is a competitive N-methyl-D-aspartate (NMDA) receptor antagonist that limits neuronal damage in animal stroke models [10].
• CSF and brain levels of CGS 19755 were 12 microM and 5 microM, respectively, at 1 h, 6 microM and 5 microM at 2 h, and 13 microM and 7 microM at 4 h [9].
• METHODS: CGS-19755 (30 mg/kg) or LY233053 (100 mg/kg) was administered 5, 30, or 60 minutes after reversible spinal cord ischemia in rabbits, induced by temporary occlusion of the infrarenal aorta [11].

Chemical compound and disease context of Selfotel

• We studied the administration of CGS 19755, nimodipine, nicardipine, and combinations of these drugs before or immediately after ischemia in globally ischemic rats [12].
• N-Methyl-D-aspartate prevented the impairment of alternation and decrease of locomotor activity produced by CGS 19755 and CPP [13].
• CGS 19755 (10 mg/kg) provided a partial protection against cisplatin-induced emesis (latency: 111 +/- 23, number of vomits and retches 30 +/- 11) [14].
• Role of hypothermia in the mechanism of protection against serotonergic toxicity. I. Experiments using 3,4-methylenedioxymethamphetamine, dizocilpine, CGS 19755 and NBQX [15].
• CGP 39551 dose-dependently inhibited locomotor activity, whereas CGS 19755 and NPC 12626 displayed a biphasic action, that is low doses inhibited locomotor activity, whereas higher doses produced mild behavioral stimulation [16].

Biological context of Selfotel

• Under these conditions, NAAG exhibits apparent inhibition constants (IC50) of 500, 790, and 8.8 microM in the kainate, AMPA, and CGS-19755 receptor binding assays, respectively [17].
• In crude P2 fractions, no evidence was obtained to suggest that CGS 19755 is taken up by an active transport system [6].
• CGS 19755 decreased tidal volume and had little effect on frequency of respiration [18].
• Glutamate and NMDA were found concentration-dependently, and in a manner that could be antagonized by CGS 19755 and MK-801, to produce cell death [19].
• The competitive excitatory amino acid antagonist cis-4-phosphonomethyl-2-piperidine-carboxylic acid (CGS 19755) increased the latency for monkeys to remove their tails from warm water (analgesia); larger doses produced ataxia, loss of righting, salivation, and eliminated reactivity to stimulation (anesthesia) [18].

Anatomical context of Selfotel

• Cortical but not basal ganglia infarct volume was significantly smaller in rats receiving CGS-19755 than in the carrier-treated group [20].
• Delayed injection (5 and 10 h postischaemia) of CGS 19755 (10 and 30 mg/kg) and MK801 (1 and 3 mg/kg) did not provide any protection against pyramidal cell loss [21].
• We conclude that CGS-19755 crosses the blood-brain barrier very slowly, even in acutely ischemic tissue [22].
• In the working memory task, CGS 19755 and 3-[(+-)-2-carboxypiperazin-4-yl]propyl-1-phosphonic acid at 10 and 32 ng/side, injected bilaterally into the dorsal hippocampus before testing, produced a significant increase in the number of errors (attempts to pass through two incorrect panels of the three panel-gates at four choice points) [23].
• Triphenyltetrazolium-determined injury volume of the ipsilateral caudate nucleus in cats treated with NPC 17742 (105 +/- 25 [SEM] mm3), MK-801 (97 +/- 22 mm3), and CGS 19755 (97 +/- 13 mm3) was less than in control cats (198 +/- 21 mm3) [24].

Associations of Selfotel with other chemical compounds

• In contrast, the NR2B H486F mutation increased the affinity of the typical antagonists CGS-19755 [(2R*,4S*)-4-phosphonomethyl-2-piperidine carboxylic acid] and 4-(3-phosphonopropyl) piperidine-2-carboxylic acid [25].
• Receptors resulting from injection of hNMDAR1A, hNMDAR2A and hNMDAR2B transcripts in a 1:1:1 ratio were indistinguishable from hNMDAR1A/2B receptors in terms of their sensitivity to NMDA, glycine, D-serine, CGS 19755 and CGP 40116 [26].
• In the present study, the influence of the prototypic anticonvulsant diphenylhydantoin (DPH) has been tested on the EEG and behavioural effects induced by the non-competitive NMDA antagonists phencyclidine (PCP) and dizocilpine (MK-801) and by the competitive NMDA antagonist cis-4-phosphonomethyl-2-piperidine-carboxylic acid (CGS 19755) [27].
• Ferrets were injected with cisplatin (10 mg/kg i.v.) and either of the non-competitive NMDA receptor antagonists dextromethorphan or memantine, or the competitive receptor antagonist CGS 19755 [14].
• Male Sprague-Dawley rats were pretreated with vehicle, CGS 19755, MK-801 or ifenprodil [28].

Gene context of Selfotel

• Also one single episode of spreading depression gave rise to a significant increase of cortical BDNF mRNA levels (to 207% of control), which was attenuated (by 61%) after administration of the competitive NMDA receptor antagonist CGS 19755 [29].
• It inhibited the binding of the selective NMDA receptor antagonist, [3H]-((+/-)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonate (CPP), with a Ki of 35 nM, and was 4, 5 and 7 fold more potent than the antagonists [+/-)-cis-4-phosphonomethylpiperidine-2-carboxylic acid) (CGS 19755), CPP and D-AP5, respectively [30].
• In the group where only CGS-19755 was used, significant neuronal protection was evident in the hippocampus (CA1 and CA3), striatum, and medial geniculate nucleus [4].
• NMDA-induced decreases in ChAT and glutamic acid decarboxylase (GAD) activities were prevented by CGS-19755 (10-40 mg/kg) and MK-801 (1-10 mg/kg) [31].
• When CGS 19755 was applied with picrotoxin, somatostatin release was the same as levels obtained in the control group with TTX [32].

Analytical, diagnostic and therapeutic context of Selfotel

• Administered before ischemia, CGS 19755 prevented calcium-calmodulin binding across all brain regions after 2 and 24 hours of reperfusion compared with controls (p less than or equal to 0.05) [12].
• No significant regional differences in plasma clearance of CGS-19755 were observed in either normal or ischemic rats except in cortex injured by electrocautery where a 14-fold increase in clearance across the blood-brain barrier was measured [22].
• The ED50 values for CGS 19755 to produce these effects (in the range of 2 mg/kg i.p.) were at least 3-fold lower than those which impaired the traction reflex, an index of motor coordination [33].
• Intravenous injections of NPC 12626 and CGS 19755 in doses up to 60 mg/kg failed to change A10 activity [34].
• Intracranial hypertension and cerebral perfusion pressure: influence on neurological deterioration and outcome in severe head injury. The Executive Committee of the International Selfotel Trial [35].

References