Loading…
The glycine transporter-1 inhibitors NFPS and Org 24461: a pharmacological study
The in vitro and in vivo pharmacology of two glycine transporter-1 (GlyT1) inhibitors, N[3-(4′-fluorophenyl)-3-(4′-phenylphenoxy)-propyl]sarcosine (NFPS) and R, S-(+/−) N-methyl- N-[(4-trifluoromethyl)phenoxy]-3-phenyl-propylglycine (Org 24461), was studied. NFPS and Org 24461 inhibited the uptake o...
Saved in:
| Published in: | Pharmacology, biochemistry and behavior biochemistry and behavior, 2003-03, Vol.74 (4), p.811-825 |
|---|---|
| Main Authors: | , , , , , , , , , , |
| Format: | Article |
| Language: | English |
| Subjects: | |
| Citations: | Items that cite this one |
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| cited_by | cdi_FETCH-LOGICAL-c488t-4c3f15235bd7df5328487afd23214b70f18f8f211fce950300a56a4da145d9e13 |
|---|---|
| cites | |
| container_end_page | 825 |
| container_issue | 4 |
| container_start_page | 811 |
| container_title | Pharmacology, biochemistry and behavior |
| container_volume | 74 |
| creator | Harsing, Laszlo G Gacsalyi, Istvan Szabo, Geza Schmidt, Eva Sziray, Nora Sebban, Claude Tesolin-Decros, Brigitte Matyus, Peter Egyed, Andras Spedding, Michael Levay, Gyorgy |
| description | The in vitro and in vivo pharmacology of two glycine transporter-1 (GlyT1) inhibitors,
N[3-(4′-fluorophenyl)-3-(4′-phenylphenoxy)-propyl]sarcosine (NFPS) and
R,
S-(+/−)
N-methyl-
N-[(4-trifluoromethyl)phenoxy]-3-phenyl-propylglycine (Org 24461), was studied. NFPS and Org 24461 inhibited the uptake of [
3H]glycine in hippocampal synaptosomal preparation with IC
50 values of 0.022 and 2.5 μM. Neither NFPS nor Org 24461 (0.1 μM) showed significant binding to α-1, α-2, and β-adrenoceptors, D
1 and D
2 dopamine receptors, and 5-HT
1A and 5-HT
2A serotonin receptors in membranes prepared from rat brain or to cloned 5-HT
6 and 5-HT
7 receptors. At 10 μM concentrations, binding affinity was measured for NFPS to 5-HT
2A and 5-HT
2C serotonin receptors and α-2 adrenoceptors and for NFPS and Org 24461 to 5-HT
7 serotonin receptors. Glycine (0.1 mM) and sarcosine (5 mM) increased [
3H]glycine efflux from superfused rat hippocampal slices preloaded with [
3H]glycine. NFPS and Org 24461 (0.1 mM) did not influence [
3H]glycine efflux, however, they inhibited glycine-induced [
3H]glycine release. These findings indicate that NFPS and Org 24461 selectively inhibit glycine uptake without being substrates of the transporter protein. Several antipsychotic tests were used to characterize antipsychotic effects of NFPS and Org 24461 in vivo. These compounds did not alter apomorphine-induced climbing and stereotypy in a dose of 10 mg/kg po in mice and did not induce catalepsy in a dose of 10 mg/kg ip in rats. The ID
50 values of NFPS were 21.4 mg/kg and higher than 30 mg/kg ip for inhibition of phencyclidine (PCP)- and
d-amphetamine-induced hypermotility in mice and these values were 2.5 and 8.6 mg/kg ip for Org 24461. NFPS and Org 24461 did not exhibit anxiolytic effects in light–dark test in mice, in the
meta-chlorophenylpiperazine (mCPP)-induced anxiety test (minimal effective dose or MED was higher than 3 mg/kg ip) and in the Vogel conflict drinking test in rats (MED was higher than 10 mg/kg ip). Both NFPS and Org 24461 (1–10 mg/kg ip) reversed PCP-induced changes in EEG power spectra in conscious rats. These data support the view that GlyT1 inhibitors may have potential importance in treatment of negative symptoms of schizophrenia. |
| doi_str_mv | 10.1016/S0091-3057(02)01078-X |
| format | article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_73148828</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S009130570201078X</els_id><sourcerecordid>20842342</sourcerecordid><originalsourceid>FETCH-LOGICAL-c488t-4c3f15235bd7df5328487afd23214b70f18f8f211fce950300a56a4da145d9e13</originalsourceid><addsrcrecordid>eNqFkE1rGzEQhkVpaRy3P6FFl5bksM2MPlbaXEIJSVsISSAp5CZkfdgq611HWgf877OxTXMMDMzleecdHkK-IPxAwPrkDqDBioNUR8COAUHp6uEdmaBWvJKo1Hsy-Y8ckMNS_gGAYLX6SA6Q1bXSjZyQ2_tFoPN241IX6JBtV1Z9HkKukKZukWZp6HOh15e3d9R2nt7kOWVC1HhKLV0tbF5a17f9PDnb0jKs_eYT-RBtW8Ln_Z6Sv5cX9-e_q6ubX3_Of15VTmg9VMLxiJJxOfPKR8mZFlrZ6BlnKGYKIuqoI0OMLjQSOICVtRXeopC-Ccin5Pvu7ir3j-tQBrNMxYW2tV3o18UojmMR02-CDLRgfJwpkTvQ5b6UHKJZ5bS0eWMQzItzs3VuXoQaYGbr3DyMua_7gvVsGfxrai95BL7tAVtGT3G07FJ55UTd1GL76dmOC6O3pxSyKS6FzgWfcnCD8X1645VnIzWbog</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>20842342</pqid></control><display><type>article</type><title>The glycine transporter-1 inhibitors NFPS and Org 24461: a pharmacological study</title><source>ScienceDirect Freedom Collection 2022-2024</source><creator>Harsing, Laszlo G ; Gacsalyi, Istvan ; Szabo, Geza ; Schmidt, Eva ; Sziray, Nora ; Sebban, Claude ; Tesolin-Decros, Brigitte ; Matyus, Peter ; Egyed, Andras ; Spedding, Michael ; Levay, Gyorgy</creator><creatorcontrib>Harsing, Laszlo G ; Gacsalyi, Istvan ; Szabo, Geza ; Schmidt, Eva ; Sziray, Nora ; Sebban, Claude ; Tesolin-Decros, Brigitte ; Matyus, Peter ; Egyed, Andras ; Spedding, Michael ; Levay, Gyorgy</creatorcontrib><description>The in vitro and in vivo pharmacology of two glycine transporter-1 (GlyT1) inhibitors,
N[3-(4′-fluorophenyl)-3-(4′-phenylphenoxy)-propyl]sarcosine (NFPS) and
R,
S-(+/−)
N-methyl-
N-[(4-trifluoromethyl)phenoxy]-3-phenyl-propylglycine (Org 24461), was studied. NFPS and Org 24461 inhibited the uptake of [
3H]glycine in hippocampal synaptosomal preparation with IC
50 values of 0.022 and 2.5 μM. Neither NFPS nor Org 24461 (0.1 μM) showed significant binding to α-1, α-2, and β-adrenoceptors, D
1 and D
2 dopamine receptors, and 5-HT
1A and 5-HT
2A serotonin receptors in membranes prepared from rat brain or to cloned 5-HT
6 and 5-HT
7 receptors. At 10 μM concentrations, binding affinity was measured for NFPS to 5-HT
2A and 5-HT
2C serotonin receptors and α-2 adrenoceptors and for NFPS and Org 24461 to 5-HT
7 serotonin receptors. Glycine (0.1 mM) and sarcosine (5 mM) increased [
3H]glycine efflux from superfused rat hippocampal slices preloaded with [
3H]glycine. NFPS and Org 24461 (0.1 mM) did not influence [
3H]glycine efflux, however, they inhibited glycine-induced [
3H]glycine release. These findings indicate that NFPS and Org 24461 selectively inhibit glycine uptake without being substrates of the transporter protein. Several antipsychotic tests were used to characterize antipsychotic effects of NFPS and Org 24461 in vivo. These compounds did not alter apomorphine-induced climbing and stereotypy in a dose of 10 mg/kg po in mice and did not induce catalepsy in a dose of 10 mg/kg ip in rats. The ID
50 values of NFPS were 21.4 mg/kg and higher than 30 mg/kg ip for inhibition of phencyclidine (PCP)- and
d-amphetamine-induced hypermotility in mice and these values were 2.5 and 8.6 mg/kg ip for Org 24461. NFPS and Org 24461 did not exhibit anxiolytic effects in light–dark test in mice, in the
meta-chlorophenylpiperazine (mCPP)-induced anxiety test (minimal effective dose or MED was higher than 3 mg/kg ip) and in the Vogel conflict drinking test in rats (MED was higher than 10 mg/kg ip). Both NFPS and Org 24461 (1–10 mg/kg ip) reversed PCP-induced changes in EEG power spectra in conscious rats. These data support the view that GlyT1 inhibitors may have potential importance in treatment of negative symptoms of schizophrenia.</description><identifier>ISSN: 0091-3057</identifier><identifier>EISSN: 1873-5177</identifier><identifier>DOI: 10.1016/S0091-3057(02)01078-X</identifier><identifier>PMID: 12667895</identifier><identifier>CODEN: PBBHAU</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>[ 3H]Glycine efflux ; [ 3H]Glycine uptake ; Amino Acid Transport Systems, Neutral - antagonists & inhibitors ; Amino Acid Transport Systems, Neutral - metabolism ; Animals ; Antipsychotic agents ; Antipsychotic tests ; Anxiolytic tests ; Biological and medical sciences ; Electroencephalogram ; Glycine - antagonists & inhibitors ; Glycine - metabolism ; Glycine Plasma Membrane Transport Proteins ; Glycine transporter-1 inhibitors ; Hippocampus - drug effects ; Hippocampus - metabolism ; Male ; Medical sciences ; Mice ; Negative symptoms of schizophrenia ; Neuropharmacology ; NFPS ; Org 24461 ; Pharmacology. Drug treatments ; Protein Binding - drug effects ; Psycholeptics: tranquillizer, neuroleptic ; Psychology. Psychoanalysis. Psychiatry ; Psychopharmacology ; Rats ; Rats, Wistar ; Sarcosine - analogs & derivatives ; Sarcosine - chemistry ; Sarcosine - pharmacology ; Stereotyped Behavior - drug effects ; Stereotyped Behavior - physiology</subject><ispartof>Pharmacology, biochemistry and behavior, 2003-03, Vol.74 (4), p.811-825</ispartof><rights>2002 Elsevier Science Inc.</rights><rights>2003 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c488t-4c3f15235bd7df5328487afd23214b70f18f8f211fce950300a56a4da145d9e13</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,783,787,27936,27937</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14696428$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12667895$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Harsing, Laszlo G</creatorcontrib><creatorcontrib>Gacsalyi, Istvan</creatorcontrib><creatorcontrib>Szabo, Geza</creatorcontrib><creatorcontrib>Schmidt, Eva</creatorcontrib><creatorcontrib>Sziray, Nora</creatorcontrib><creatorcontrib>Sebban, Claude</creatorcontrib><creatorcontrib>Tesolin-Decros, Brigitte</creatorcontrib><creatorcontrib>Matyus, Peter</creatorcontrib><creatorcontrib>Egyed, Andras</creatorcontrib><creatorcontrib>Spedding, Michael</creatorcontrib><creatorcontrib>Levay, Gyorgy</creatorcontrib><title>The glycine transporter-1 inhibitors NFPS and Org 24461: a pharmacological study</title><title>Pharmacology, biochemistry and behavior</title><addtitle>Pharmacol Biochem Behav</addtitle><description>The in vitro and in vivo pharmacology of two glycine transporter-1 (GlyT1) inhibitors,
N[3-(4′-fluorophenyl)-3-(4′-phenylphenoxy)-propyl]sarcosine (NFPS) and
R,
S-(+/−)
N-methyl-
N-[(4-trifluoromethyl)phenoxy]-3-phenyl-propylglycine (Org 24461), was studied. NFPS and Org 24461 inhibited the uptake of [
3H]glycine in hippocampal synaptosomal preparation with IC
50 values of 0.022 and 2.5 μM. Neither NFPS nor Org 24461 (0.1 μM) showed significant binding to α-1, α-2, and β-adrenoceptors, D
1 and D
2 dopamine receptors, and 5-HT
1A and 5-HT
2A serotonin receptors in membranes prepared from rat brain or to cloned 5-HT
6 and 5-HT
7 receptors. At 10 μM concentrations, binding affinity was measured for NFPS to 5-HT
2A and 5-HT
2C serotonin receptors and α-2 adrenoceptors and for NFPS and Org 24461 to 5-HT
7 serotonin receptors. Glycine (0.1 mM) and sarcosine (5 mM) increased [
3H]glycine efflux from superfused rat hippocampal slices preloaded with [
3H]glycine. NFPS and Org 24461 (0.1 mM) did not influence [
3H]glycine efflux, however, they inhibited glycine-induced [
3H]glycine release. These findings indicate that NFPS and Org 24461 selectively inhibit glycine uptake without being substrates of the transporter protein. Several antipsychotic tests were used to characterize antipsychotic effects of NFPS and Org 24461 in vivo. These compounds did not alter apomorphine-induced climbing and stereotypy in a dose of 10 mg/kg po in mice and did not induce catalepsy in a dose of 10 mg/kg ip in rats. The ID
50 values of NFPS were 21.4 mg/kg and higher than 30 mg/kg ip for inhibition of phencyclidine (PCP)- and
d-amphetamine-induced hypermotility in mice and these values were 2.5 and 8.6 mg/kg ip for Org 24461. NFPS and Org 24461 did not exhibit anxiolytic effects in light–dark test in mice, in the
meta-chlorophenylpiperazine (mCPP)-induced anxiety test (minimal effective dose or MED was higher than 3 mg/kg ip) and in the Vogel conflict drinking test in rats (MED was higher than 10 mg/kg ip). Both NFPS and Org 24461 (1–10 mg/kg ip) reversed PCP-induced changes in EEG power spectra in conscious rats. These data support the view that GlyT1 inhibitors may have potential importance in treatment of negative symptoms of schizophrenia.</description><subject>[ 3H]Glycine efflux</subject><subject>[ 3H]Glycine uptake</subject><subject>Amino Acid Transport Systems, Neutral - antagonists & inhibitors</subject><subject>Amino Acid Transport Systems, Neutral - metabolism</subject><subject>Animals</subject><subject>Antipsychotic agents</subject><subject>Antipsychotic tests</subject><subject>Anxiolytic tests</subject><subject>Biological and medical sciences</subject><subject>Electroencephalogram</subject><subject>Glycine - antagonists & inhibitors</subject><subject>Glycine - metabolism</subject><subject>Glycine Plasma Membrane Transport Proteins</subject><subject>Glycine transporter-1 inhibitors</subject><subject>Hippocampus - drug effects</subject><subject>Hippocampus - metabolism</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Negative symptoms of schizophrenia</subject><subject>Neuropharmacology</subject><subject>NFPS</subject><subject>Org 24461</subject><subject>Pharmacology. Drug treatments</subject><subject>Protein Binding - drug effects</subject><subject>Psycholeptics: tranquillizer, neuroleptic</subject><subject>Psychology. Psychoanalysis. Psychiatry</subject><subject>Psychopharmacology</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Sarcosine - analogs & derivatives</subject><subject>Sarcosine - chemistry</subject><subject>Sarcosine - pharmacology</subject><subject>Stereotyped Behavior - drug effects</subject><subject>Stereotyped Behavior - physiology</subject><issn>0091-3057</issn><issn>1873-5177</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><recordid>eNqFkE1rGzEQhkVpaRy3P6FFl5bksM2MPlbaXEIJSVsISSAp5CZkfdgq611HWgf877OxTXMMDMzleecdHkK-IPxAwPrkDqDBioNUR8COAUHp6uEdmaBWvJKo1Hsy-Y8ckMNS_gGAYLX6SA6Q1bXSjZyQ2_tFoPN241IX6JBtV1Z9HkKukKZukWZp6HOh15e3d9R2nt7kOWVC1HhKLV0tbF5a17f9PDnb0jKs_eYT-RBtW8Ln_Z6Sv5cX9-e_q6ubX3_Of15VTmg9VMLxiJJxOfPKR8mZFlrZ6BlnKGYKIuqoI0OMLjQSOICVtRXeopC-Ccin5Pvu7ir3j-tQBrNMxYW2tV3o18UojmMR02-CDLRgfJwpkTvQ5b6UHKJZ5bS0eWMQzItzs3VuXoQaYGbr3DyMua_7gvVsGfxrai95BL7tAVtGT3G07FJ55UTd1GL76dmOC6O3pxSyKS6FzgWfcnCD8X1645VnIzWbog</recordid><startdate>20030301</startdate><enddate>20030301</enddate><creator>Harsing, Laszlo G</creator><creator>Gacsalyi, Istvan</creator><creator>Szabo, Geza</creator><creator>Schmidt, Eva</creator><creator>Sziray, Nora</creator><creator>Sebban, Claude</creator><creator>Tesolin-Decros, Brigitte</creator><creator>Matyus, Peter</creator><creator>Egyed, Andras</creator><creator>Spedding, Michael</creator><creator>Levay, Gyorgy</creator><general>Elsevier Inc</general><general>Elsevier Science</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7TK</scope><scope>7X8</scope></search><sort><creationdate>20030301</creationdate><title>The glycine transporter-1 inhibitors NFPS and Org 24461: a pharmacological study</title><author>Harsing, Laszlo G ; Gacsalyi, Istvan ; Szabo, Geza ; Schmidt, Eva ; Sziray, Nora ; Sebban, Claude ; Tesolin-Decros, Brigitte ; Matyus, Peter ; Egyed, Andras ; Spedding, Michael ; Levay, Gyorgy</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c488t-4c3f15235bd7df5328487afd23214b70f18f8f211fce950300a56a4da145d9e13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>[ 3H]Glycine efflux</topic><topic>[ 3H]Glycine uptake</topic><topic>Amino Acid Transport Systems, Neutral - antagonists & inhibitors</topic><topic>Amino Acid Transport Systems, Neutral - metabolism</topic><topic>Animals</topic><topic>Antipsychotic agents</topic><topic>Antipsychotic tests</topic><topic>Anxiolytic tests</topic><topic>Biological and medical sciences</topic><topic>Electroencephalogram</topic><topic>Glycine - antagonists & inhibitors</topic><topic>Glycine - metabolism</topic><topic>Glycine Plasma Membrane Transport Proteins</topic><topic>Glycine transporter-1 inhibitors</topic><topic>Hippocampus - drug effects</topic><topic>Hippocampus - metabolism</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Negative symptoms of schizophrenia</topic><topic>Neuropharmacology</topic><topic>NFPS</topic><topic>Org 24461</topic><topic>Pharmacology. Drug treatments</topic><topic>Protein Binding - drug effects</topic><topic>Psycholeptics: tranquillizer, neuroleptic</topic><topic>Psychology. Psychoanalysis. Psychiatry</topic><topic>Psychopharmacology</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Sarcosine - analogs & derivatives</topic><topic>Sarcosine - chemistry</topic><topic>Sarcosine - pharmacology</topic><topic>Stereotyped Behavior - drug effects</topic><topic>Stereotyped Behavior - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Harsing, Laszlo G</creatorcontrib><creatorcontrib>Gacsalyi, Istvan</creatorcontrib><creatorcontrib>Szabo, Geza</creatorcontrib><creatorcontrib>Schmidt, Eva</creatorcontrib><creatorcontrib>Sziray, Nora</creatorcontrib><creatorcontrib>Sebban, Claude</creatorcontrib><creatorcontrib>Tesolin-Decros, Brigitte</creatorcontrib><creatorcontrib>Matyus, Peter</creatorcontrib><creatorcontrib>Egyed, Andras</creatorcontrib><creatorcontrib>Spedding, Michael</creatorcontrib><creatorcontrib>Levay, Gyorgy</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Pharmacology, biochemistry and behavior</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Harsing, Laszlo G</au><au>Gacsalyi, Istvan</au><au>Szabo, Geza</au><au>Schmidt, Eva</au><au>Sziray, Nora</au><au>Sebban, Claude</au><au>Tesolin-Decros, Brigitte</au><au>Matyus, Peter</au><au>Egyed, Andras</au><au>Spedding, Michael</au><au>Levay, Gyorgy</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The glycine transporter-1 inhibitors NFPS and Org 24461: a pharmacological study</atitle><jtitle>Pharmacology, biochemistry and behavior</jtitle><addtitle>Pharmacol Biochem Behav</addtitle><date>2003-03-01</date><risdate>2003</risdate><volume>74</volume><issue>4</issue><spage>811</spage><epage>825</epage><pages>811-825</pages><issn>0091-3057</issn><eissn>1873-5177</eissn><coden>PBBHAU</coden><abstract>The in vitro and in vivo pharmacology of two glycine transporter-1 (GlyT1) inhibitors,
N[3-(4′-fluorophenyl)-3-(4′-phenylphenoxy)-propyl]sarcosine (NFPS) and
R,
S-(+/−)
N-methyl-
N-[(4-trifluoromethyl)phenoxy]-3-phenyl-propylglycine (Org 24461), was studied. NFPS and Org 24461 inhibited the uptake of [
3H]glycine in hippocampal synaptosomal preparation with IC
50 values of 0.022 and 2.5 μM. Neither NFPS nor Org 24461 (0.1 μM) showed significant binding to α-1, α-2, and β-adrenoceptors, D
1 and D
2 dopamine receptors, and 5-HT
1A and 5-HT
2A serotonin receptors in membranes prepared from rat brain or to cloned 5-HT
6 and 5-HT
7 receptors. At 10 μM concentrations, binding affinity was measured for NFPS to 5-HT
2A and 5-HT
2C serotonin receptors and α-2 adrenoceptors and for NFPS and Org 24461 to 5-HT
7 serotonin receptors. Glycine (0.1 mM) and sarcosine (5 mM) increased [
3H]glycine efflux from superfused rat hippocampal slices preloaded with [
3H]glycine. NFPS and Org 24461 (0.1 mM) did not influence [
3H]glycine efflux, however, they inhibited glycine-induced [
3H]glycine release. These findings indicate that NFPS and Org 24461 selectively inhibit glycine uptake without being substrates of the transporter protein. Several antipsychotic tests were used to characterize antipsychotic effects of NFPS and Org 24461 in vivo. These compounds did not alter apomorphine-induced climbing and stereotypy in a dose of 10 mg/kg po in mice and did not induce catalepsy in a dose of 10 mg/kg ip in rats. The ID
50 values of NFPS were 21.4 mg/kg and higher than 30 mg/kg ip for inhibition of phencyclidine (PCP)- and
d-amphetamine-induced hypermotility in mice and these values were 2.5 and 8.6 mg/kg ip for Org 24461. NFPS and Org 24461 did not exhibit anxiolytic effects in light–dark test in mice, in the
meta-chlorophenylpiperazine (mCPP)-induced anxiety test (minimal effective dose or MED was higher than 3 mg/kg ip) and in the Vogel conflict drinking test in rats (MED was higher than 10 mg/kg ip). Both NFPS and Org 24461 (1–10 mg/kg ip) reversed PCP-induced changes in EEG power spectra in conscious rats. These data support the view that GlyT1 inhibitors may have potential importance in treatment of negative symptoms of schizophrenia.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>12667895</pmid><doi>10.1016/S0091-3057(02)01078-X</doi><tpages>15</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0091-3057 |
| ispartof | Pharmacology, biochemistry and behavior, 2003-03, Vol.74 (4), p.811-825 |
| issn | 0091-3057 1873-5177 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_73148828 |
| source | ScienceDirect Freedom Collection 2022-2024 |
| subjects | [ 3H]Glycine efflux [ 3H]Glycine uptake Amino Acid Transport Systems, Neutral - antagonists & inhibitors Amino Acid Transport Systems, Neutral - metabolism Animals Antipsychotic agents Antipsychotic tests Anxiolytic tests Biological and medical sciences Electroencephalogram Glycine - antagonists & inhibitors Glycine - metabolism Glycine Plasma Membrane Transport Proteins Glycine transporter-1 inhibitors Hippocampus - drug effects Hippocampus - metabolism Male Medical sciences Mice Negative symptoms of schizophrenia Neuropharmacology NFPS Org 24461 Pharmacology. Drug treatments Protein Binding - drug effects Psycholeptics: tranquillizer, neuroleptic Psychology. Psychoanalysis. Psychiatry Psychopharmacology Rats Rats, Wistar Sarcosine - analogs & derivatives Sarcosine - chemistry Sarcosine - pharmacology Stereotyped Behavior - drug effects Stereotyped Behavior - physiology |
| title | The glycine transporter-1 inhibitors NFPS and Org 24461: a pharmacological study |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-11-13T08%3A39%3A18IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20glycine%20transporter-1%20inhibitors%20NFPS%20and%20Org%2024461:%20a%20pharmacological%20study&rft.jtitle=Pharmacology,%20biochemistry%20and%20behavior&rft.au=Harsing,%20Laszlo%20G&rft.date=2003-03-01&rft.volume=74&rft.issue=4&rft.spage=811&rft.epage=825&rft.pages=811-825&rft.issn=0091-3057&rft.eissn=1873-5177&rft.coden=PBBHAU&rft_id=info:doi/10.1016/S0091-3057(02)01078-X&rft_dat=%3Cproquest_cross%3E20842342%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c488t-4c3f15235bd7df5328487afd23214b70f18f8f211fce950300a56a4da145d9e13%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=20842342&rft_id=info:pmid/12667895&rfr_iscdi=true |