Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The manipulation of glutamate neurotransmission could represent a potential strategy for the pharmacotherapy of schizophrenic symptoms. Preclinical studies suggest that two subtypes of metabotropic glutamate (mGlu) receptors such as mGlu2/3 and mGlu5 receptors have the potential to ameliorate deficits in schizophrenia. In our study we evaluated the role of a non-specific mGlu receptor agonist ((1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid; 1S,3R-ACPD), mGlu5 receptor agonist or positive modulators ((RS)-2-Chloro-5-hydroxyphenylglycine;CHPG; [(3-Fluoro-phenyl)methylene]hydrazone-3-fluorobenzaldehyde; DFB; 3-Cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide; CDPPB) and a mGlu2/3 receptor agonist (2,2,2-Trifluoro-N-[4-(2-methoxyphenoxy)phenyl]-N-(3-pyrdinylmethyl)ethanesulfonamide hydrochloride; LY-487379) on performance in a cognitive task (Active Allothetic Place Avoidance) after sub-chronic administration of 5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)-cyclo-hepten-5,10-imine; MK-801 . The Active Allothetic Place Avoidance task is suitable for assessing the executive function and attention of animals and was previously validated for testing the effect of anti-psychotics. Application of the mGlu2/3 receptor agonist had no effect on cognitive impairment induced by MK-801. However, the mGlu5 receptor agonists ameliorated cognitive impairment induced by MK-801 without affecting locomotion. In conclusion, the mGlu5 receptor agonists could be effective in the treatment of cognitive deficits in patients with schizophrenia. However, the pro-cognitive effect of the agonist of mGlu2/3 receptors was not demonstrated in the present study.
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PMID:The difference in effect of mGlu2/3 and mGlu5 receptor agonists on cognitive impairment induced by MK-801. 2037 Dec 26

Drugs that interact with group II metabotropic glutamate receptors (mGluRs) are presently being evaluated for a role in the treatment of anxiety disorders and symptoms of schizophrenia. Their mechanism of action is believed to involve a reduction in excitatory neurotransmission in limbic and forebrain regions commonly associated with these mental disorders. In rodents, the glutamatergic neurons in the midline paraventricular thalamic nucleus (PVT) provide excitatory inputs to the limbic system and forebrain. PVT also displays a high density of group II mGluRs, predominantly the metabotropic glutamate 2 receptor (mGluR2). Because the role of group II mGluRs in regulating cellular and synaptic excitability in this location has yet to be determined, we used whole-cell patch-clamp recording and acute rat brain slice preparations to evaluate PVT neuron responses to a selective group II mGluR agonist, (1R,4R,5S,6R)-4-amino-2-oxabicyclo[3.1.0]hexane-4,6-dicarboxylic acid (LY 379268). LY 379268 consistently induced membrane hyperpolarization and suppressed firing by postsynaptic receptor-mediated activation of a barium-sensitive background K(+) conductance. This effect could be blocked by (2S)-2-amino-2-[(1S,2S)-2-carboxycycloprop-1-yl]-3-(xanth-9-yl)propanoic acid (LY 341495), a selective group II mGluR antagonist. In addition, LY 379268 acted at presynaptic receptors to reduce ionotropic glutamate receptor-mediated excitatory synaptic transmission. An mGluR2-positive allosteric modulator, 2,2,2-trifluoro-N-[4-(2-methoxyphenoxy)phenyl]-N-(3-pyridinylmethyl)ethanesulfonamide hydrochloride (LY 487379), resulted in leftward shifts of the LY 379268 dose-response curve for both postsynaptic and presynaptic actions. The data demonstrate that activation of postsynaptic and presynaptic group II (presumably mGluR2) mGluRs reduces neuronal excitability in midline thalamus, an action that may contribute to the effectiveness of mGluR2-activating drugs in rodent models of anxiety and psychosis.
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PMID:Postsynaptic and presynaptic group II metabotropic glutamate receptor activation reduces neuronal excitability in rat midline paraventricular thalamic nucleus. 2113 59