Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.16.2 (PCP)
 3,761 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ion entry into neurons occurs either through receptor-operated channels (ROC) or voltage-operated channels (VOC). The function of ROC depends crucially on the action of agonists, antagonists or compounds modulating particular types of receptors (GABA A, NMDA, Ach N receptors). The function of VOC is closely connected with the activity of protein kinases and the processes of phosphorylation of membrane proteins (K+, Na+, Ca2+ channels). Gamma aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the vertebrate brain. The GABA A receptor is a oligomeric complex of multiple binding sites and chloride channel. This complex contains recognition sites for GABA, anxiolytics such as benzodiazepine, anxiogenic--beta-carboline, and convulsant such as picrotoxin. Chloride ion channel plays a crucial role in anxiogenic, anxiolytic and convulsant activities. Glutamic acid is the main endogenous neurotransmitter for N-methyl-D-aspartate (NMDA)-type excitatory amino acid receptor. NMDA receptors connected with Ca2+ channel, have multiple modulatory sites which are affected by a wide range of compounds. There are NMDA and competitive NMDA antagonists site, the glycine site, the phencyclidine (PCP) site and the binding site of Mg2+ ions in this receptor complex. Calcium entry through NMDA receptors may be important in the etiology of many psychiatric disorders. VOC mediate rapid, voltage-gated changes in ion permeability during action potentials in neurons. Electrophysiological studies indicate the existence of three types of VOC (K+, Na+, Ca2+ channels). In number of neurons various subtypes of Ca2+ channels (P, T, N and L-type) occur together. Among them, the L-type calcium channel has been first described and most thoroughly studied. The L-type calcium channel is localized on nerve terminals in the pre and postsynaptic parts, as well as on cell bodies and may be involved in the mechanism of action of psychotropic drugs. Chronic treatment with various psychotropic drugs changes the density of voltage-dependent Ca2+ channels in the central nervous system. Thus calcium entry through both VOC and ROC may be important in the etiology of many psychiatric disorders.
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PMID:Receptor and voltage-operated ion channels in the central nervous system. 871 58

A dextromethorphan (3-methoxy-17-methylmorphinan) analog, dimemorfan (3-methyl-N-methylmorphinan) that is not metabolized to dextrorphan [3-hydroxy-17-methylmorphinan, which induces phencyclidine (PCP)-like behavioral effects], attenuates maximal electroshock seizures. However, the pharmacological mechanism of action of dimemorfan remains to be determined. In this study, we assessed the locomotor activity mediated by these morphinans. Circling behavior was pronounced in mice treated with PCP or dextrorphan, while animals treated with dextromethorphan exhibited moderate behaviors. Dimemorfan did not show any significant behavioral effects. We used BAY k-8644 (an L-type Ca2+ channel agonist in the dihydropyridine class) to explore the effects of dextromethorphan and dimemorfan on the convulsant activity regulated by calcium channels. Intracerebroventricular injection of BAY k-8644 (37.5 microg) significantly induced seizures in mice. As with dextromethorphan (6.25 or 12.5 mg/kg), dimemorfan (6.25 or 12.5 mg/kg) pretreatment significantly attenuated BAY k-8644-induced seizures in a dose-dependent manner. BAY k-8644-induced seizure activity paralleled increased expression of c-fos and c-jun, AP-1 DNA binding activity, and fos-related antigen immunoreactivity. Pretreatment with dextromethorphan or dimemorfan significantly attenuated the expression induced by BAY k-8644. Therefore, our results suggest that the anticonvulsant effects of dextromethorphan and dimemorfan are mediated, at least in part, via L-type calcium channel, and that dimemorfan is equipotent to dextromethorphan in preventing BAY k-8644-induced seizures, while it lacks behavioral side effects related to psychotomimetic reactions.
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PMID:Dimemorfan prevents seizures induced by the L-type calcium channel activator BAY k-8644 in mice. 1508 42