VDCCs and NMDARs underlie two forms of LTP in CA1 hippocampus in vivo.
Animals; Calcium Channel Blockers/*pharmacology; Dizocilpine Maleate/pharmacology; Excitatory Amino Acid Antagonists/*pharmacology; Excitatory Postsynaptic Potentials/drug effects; Hippocampus/*drug effects; Long-Evans; Long-Term Potentiation/*drug effects; Male; Membrane Potentials/physiology; N-Methyl-D-Aspartate/*antagonists & inhibitors; Rats; Receptors; Verapamil/pharmacology
N-methyl-D-aspartate receptor/channel (NMDAR) and voltage-dependent calcium channel (VDCC) antagonists applied independently reduce the magnitude of long-term potentiation (LTP) in area CA1 of the hippocampal slice preparation. When used in combination, the antagonists completely block the induction of LTP. In urethan-anesthetized rats we examined the effect of the NMDAR blocker MK-801 (0.1 mg/kg) and the VDCC blocker Verapamil (10 mg/kg) on LTP induction in area CA1. Extracellular recordings were obtained from stratum radiatum following stimulation of Schaffer collaterals. LTP was induced by a 200-Hz/100-ms tetanus repeated 10 times (2 s isi). Tetanus was given in the presence of intraperitoneal saline, MK-801, Verapamil, or both Verapamil and MK-801. When given separately, Verapamil and MK-801 both significantly reduced the magnitude of LTP as compared with control animals. When given together, the drugs blocked the induction of LTP completely. We conclude that like LTP in vitro, VDCCs and NMDAR underlie two forms of LTP in vivo.
Morgan S L; Teyler T J
Journal of neurophysiology
1999
1999-08
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1152/jn.1999.82.2.736" target="_blank" rel="noreferrer noopener">10.1152/jn.1999.82.2.736</a>
Development and validation of an LC-MS/MS method for determination of the L-type voltage-gated calcium channel/NMDA receptor antagonist NGP1-01 in mouse serum.
Animals; Bridged-Ring Compounds/*blood; Calcium Channel Blockers/*blood; Chromatography; LC-MS/MS; Limit of Detection; Liquid/*methods; Mice; Mouse serum; Multifunctional drug; N-Methyl-D-Aspartate/*antagonists & inhibitors; Neuroprotective agent; NGP1-01; Pentacycloundecylamine; Receptors; Reproducibility of Results; Tandem Mass Spectrometry/*methods
NGP1-01 (8-benzylamino-8,11-oxapentacyclo[5.4.0.0(2,6).0(3,10).0(5,9)]undecane) is a heterocyclic cage compound with multifunctional calcium channel blocking activity that has been demonstrated to be neuroprotective in several neurodegenerative models. A sensitive internal standard LC-MS/MS method was developed and validated to quantify NGP1-01 in mouse serum. The internal standard (IS) was
Jogiraju Harini; Zhou Xiang; Gobburi Ashta Lakshmi Prasad; Pedada Kiran K; Geldenhuys Werner J; Van der Schyf Cornelis J; Crish Samuel D; Anderson David J
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences
2014
2014-07
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.jchromb.2014.05.048" target="_blank" rel="noreferrer noopener">10.1016/j.jchromb.2014.05.048</a>
Structure-activity relationships of pentacycloundecylamines at the
Amines/chemical synthesis/chemistry/*pharmacology; Animals; Brain/drug effects; Dizocilpine Maleate/pharmacology; Excitatory Amino Acid Antagonists/*pharmacology; Inbred ICR; Ion Channels; Male; Mice; Models; Molecular; N-Methyl-D-Aspartate/*antagonists & inhibitors; Phencyclidine/analogs & derivatives; Piperidines/pharmacology; Radioligand Assay; Receptors; Structure-Activity Relationship; Synaptosomes/*drug effects; Thiophenes/pharmacology
Prompted by our interest in neuroprotective agents with multiple mechanisms of action, we assessed the structure-activity relationship of a series of pentacycloundecylamine derivatives previously shown to have both L-type calcium channel blocking activity and N-methyl-d-aspartate receptor (NMDAR) antagonistic activity. We utilized a functional assay to measure NMDAR channel block using (45)Ca(2+) influx into synaptoneurosomes. The cage amine
Geldenhuys Werner J; Malan Sarel F; Bloomquist Jeffrey R; Van der Schyf Cornelis J
Bioorganic & medicinal chemistry
2007
2007-02
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.bmc.2006.09.060" target="_blank" rel="noreferrer noopener">10.1016/j.bmc.2006.09.060</a>