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  • 1
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    Response: is ethanol antagonist rol5-4513 selective for ethanol? (1988)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1988-02-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Suzdak, P D -- Glowa, J R -- Crawley, J N -- Skolnick, P -- Paul, S M -- New York, N.Y. -- Science. 1988 Feb 5;239(4840):649-50.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17759061" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    Inosine may be an endogenous ligand for benzodiazepine receptors on cultured spinal neurons (1979)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1979-08-17
    Description: Mouse spinal neurons grown in tissue culture were used to study the membrane effects of the benzodiazepine flurazepam and the naturally occurring purine nucleoside inosine, which competes for benzodiazepine receptor sites in the central nervous system. Application of inosine elicited two types of transmitter-like membrane effects: a rapidly desensitizing excitatory response and a nondesensitizing inhibitory response. Flurazepam produced a similar excitatory response which showed cross-desensitization with the purine excitation. Flurazepam also blocked the inhibitory inosine response. The results provide electrophysiological evidence that an endogenous purine can activate two different conductances on spinal neurons and that flurazepam can activate one of the conductances and antagonize the other.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉MacDonald, J F -- Barker, J L -- Paul, S M -- Marangos, P J -- Skolnick, P -- New York, N.Y. -- Science. 1979 Aug 17;205(4407):715-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/37602" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Benzodiazepines/*metabolism ; Cells, Cultured ; Electric Conductivity ; Flurazepam/antagonists & inhibitors ; Inosine/*metabolism/pharmacology ; Ligands ; Mice ; Neurotransmitter Agents/metabolism ; Receptors, Drug/*metabolism ; Receptors, Neurotransmitter/metabolism ; Spinal Cord/*metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
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    Pentobarbital: dual actions to increase brain benzodiazepine receptor affinity (1981)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1981-03-27
    Description: The binding of [3H]diazepam to benzodiazepine receptors was studied in extensively washed membranes of rat cerebral cortex in the presence of the depressant barbiturate, pentobarbital. Pentobarbital, like the endogenous neurotransmitter gamma-aminobutyric acid (GABA), increased the basal binding and also potentiated the GABA-enhanced binding of [3H]diazepam to benzodiazepine receptors by increasing the apparent affinity of [3H]diazepam for the benzodiazepine receptor. The concentrations of pentobarbital necessary to elicit these effects in vitro are the same as those observed after treatment with pharmacologically relevant doses, suggesting that a common neurochemical association may exist between these types of compounds.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Skolnick, P -- Moncada, V -- Barker, J L -- Paul, S M -- New York, N.Y. -- Science. 1981 Mar 27;211(4489):1448-50.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6258230" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cerebral Cortex/drug effects ; Chlorides/metabolism ; Diazepam/metabolism ; Male ; Pentobarbital/*pharmacology ; Rats ; Receptors, Drug/*drug effects/metabolism ; Receptors, GABA-A ; Stimulation, Chemical ; gamma-Aminobutyric Acid/pharmacology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
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    Benzodiazepine receptor-mediated experimental "anxiety" in primates (1982)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1982-12-24
    Description: The ethyl ester of beta-carboline-3-carboxylic acid has a high affinity for benzodiazepine receptors in the brain. In the rhesus monkey this substance produces an acute behavioral syndrome characterized by dramatic elevations in heart rate, blood pressure, plasma cortisol, and catecholamines. The effects are blocked by benzodiazepines and the specific benzodiazepine receptor antagonist Ro 15-1788. The benzodiazepine receptor may consist of several subsites or functional domains that independently recognize agonist, antagonists, or "active" antagonists such as beta-carboline-3-carboxylic acid ethyl ester. These results suggest that the benzodiazepine receptor is involved in both the affective and physiological manifestations of anxiety, and that the administration of beta-carboxylic acid ethyl ester to monkeys may provide a reliable and reproducible animal model of human anxiety.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ninan, P T -- Insel, T M -- Cohen, R M -- Cook, J M -- Skolnick, P -- Paul, S M -- New York, N.Y. -- Science. 1982 Dec 24;218(4579):1332-4.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6293059" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anxiety/*etiology ; Benzodiazepinones ; Blood Pressure/drug effects ; Carbolines/pharmacology ; *Disease Models, Animal ; Epinephrine/pharmacology ; Flumazenil ; Heart Rate/*drug effects ; Humans ; Hydrocortisone/blood ; Macaca mulatta ; Male ; Norepinephrine/pharmacology ; Receptors, Drug/*physiology ; Receptors, GABA-A
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
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    A benzodiazepine receptor antagonist decreases sleep and reverses the hypnotic actions of flurazepam (1983)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1983-01-28
    Description: The benzodiazepine receptor antagonist 3-hydroxymethyl-beta-carboline, which blocks several of the pharmacological actions of benzodiazepines, induces a dose-dependent increase in sleep latency in the rat. Furthermore, at a low dose that by itself does not affect sleep, 3-hydroxymethyl-beta-carboline blocks sleep induction by a large dose of flurazepam. The benzodiazepine receptor may play a role in both the physiological regulation and pharmacological induction of sleep.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mendelson, W B -- Cain, M -- Cook, J M -- Paul, S M -- Skolnick, P -- New York, N.Y. -- Science. 1983 Jan 28;219(4583):414-6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6294835" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Carbolines/*pharmacology ; Flurazepam/*antagonists & inhibitors ; Indoles/*pharmacology ; Male ; Rats ; Receptors, Cell Surface/*drug effects ; Receptors, GABA-A ; Sleep/*drug effects ; Wakefulness/drug effects
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 6
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    Rapid changes in brain benzodiazepine receptors after experimental seizures (1978)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1978-11-24
    Description: Seizures induced in the rat by electroshock or by injections of pentylenetetrazol increase the specific binding of diazepam to putative receptor sites in cerebral cortical membranes. The enhancement of diazepam binding results from a rapid increase in the number of available binding sites rather than a change in receptor affinity. The postictal increase in cortical benzodiazepine receptors suggests that the cerebral cortex might be more sensitive to the anticonvulsant effects of the benzodiazepines after seizures. This observation may be related to the mechanism of action of these drugs in the treatment of recurrent seizures such as status epilepticus.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Paul, S M -- Skolnick, P -- New York, N.Y. -- Science. 1978 Nov 24;202(4370):892-4.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/715447" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anoxia/metabolism ; Binding Sites ; Brain/*metabolism ; Cerebral Cortex/metabolism ; Diazepam/*metabolism ; Electroshock ; Kinetics ; Male ; Pentylenetetrazole ; Rats ; Receptors, Drug/*metabolism ; Seizures/*metabolism ; Synaptosomes/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
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    (+)-Amphetamine binding to rat hypothalamus: relation to anorexic potency for phenylethylamines (1982)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1982-10-29
    Description: Saturable and stereospecific binding sites for (+)-[3H]amphetamine were demonstrated in membrane preparations from rat brain. The density of these binding sites varies among brain regions and is highest in the hypothalamus and brainstem. Specific (+)-[3H]amphetamine binding in hypothalamus is largely confined to synaptosomal membranes, rapidly reversible, and sensitive to both heat and proteolytic enzymes. Scatchard analysis of the equilibrium binding data revealed two distinct sites with apparent affinity constants of 93 and 300 nanomoles per liter, respectively. The effects of various psychotropic drugs as well as a number of putative neurotransmitters and related agonists and antagonists in displacing specific (+)-[3H]amphetamine binding demonstrate that these binding sites are not associated with any previously described neurotransmitter or drug receptors, but are specific for amphetamine and related phenylethylamine derivatives. Furthermore, the relative affinities of a series of phenylethylamine derivatives for (+)-[3H]amphetamine binding sites in hypothalamic membranes is highly correlated to their potencies as anorexic agents. These results suggest the presence of specific receptor sites in hypothalamus that mediate the anorexic activity of amphetamine and related drugs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Paul, S M -- Hulihan-Giblin, B -- Skolnick, P -- New York, N.Y. -- Science. 1982 Oct 29;218(4571):487-90.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7123250" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anorexia/physiopathology ; Appetite Depressants/*pharmacology ; Cell Membrane/metabolism ; Dextroamphetamine/*metabolism ; Hypothalamus/drug effects/*metabolism/physiology ; Male ; Phenethylamines/metabolism ; Rats ; Receptors, Drug/*metabolism ; Structure-Activity Relationship
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 8
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    Interaction between purine and benzodiazepine: Inosine reverses diazepam-induced stimulation of mouse exploratory behavior (1981)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1981-02-13
    Description: Inosine, 2-deoxyinosine, and 2-deoxyguanosine completely reversed the increase in exploratory activity elicited in mice by diazepam. The inhibition of exploratory behavior by purines occurred at doses that when given alone have no effect on exploratory behavior. 7-Methylinosine, which does not bind to the brain benzodiazepine binding site in vitro, had no effect on the diazepam-induced increase in exploratory behavior. Behavioral effects produced by various combinations of inosine and diazepam indicate that the interaction between purine and benzodiazepine is antagonistic and support the hypothesis that the naturally occurring purines function in anxiety-related behaviors that respond to benzodiazepine treatment.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Crawley, J N -- Marangos, P J -- Paul, S M -- Skolnick, P -- Goodwin, F K -- New York, N.Y. -- Science. 1981 Feb 13;211(4483):725-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6256859" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anxiety/*drug effects ; Behavior, Animal/drug effects ; Diazepam/*antagonists & inhibitors ; Dose-Response Relationship, Drug ; Humans ; Inosine/*pharmacology ; Male ; Mice ; Receptors, Drug/*drug effects ; Receptors, GABA-A
    Print ISSN: 0036-8075
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  • 9
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    Receptors for the age of anxiety: pharmacology of the benzodiazepines (1980)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1980-01-18
    Description: Investigation of the actions of the benzodiazepines has provided insights into the neurochemical mechanisms underlying anxiety, seizures, muscle relaxation, and sedation. Behavioral, electrophysical, pharmacological, and biochemical evidence indicates that the benzodiazepines exert their therapeutic effects by interacting with a high-affinity binding site (receptor) in the brain. The benzodiazepine receptor interacts with a receptor for gamma-aminobutyric acid, a major inhibitory neurotransmitter, and enhances its inhibitory effects. The benzodiazepine receptor may also interact with endogenous substances and several naturally occurring compounds, including the purines and nicotinamide, are candidates for this role. Both the purines and nicotinamide possess some benzodiazepine-like properties in vivo, although further work will be required to confirm their possible roles as endogenous benzodiazepines.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tallman, J F -- Paul, S M -- Skolnick, P -- Gallager, D W -- New York, N.Y. -- Science. 1980 Jan 18;207(4428):274-81.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6101294" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anti-Anxiety Agents/*pharmacology ; Anticonvulsants ; Anxiety/physiopathology ; Benzodiazepines ; Brain/physiology ; Humans ; Ion Channels/drug effects ; Ligands ; Muscle Relaxation/drug effects ; Neural Inhibition/drug effects ; Receptors, Drug/*physiology ; Receptors, Neurotransmitter/drug effects ; Synaptic Transmission/drug effects ; Temperature ; gamma-Aminobutyric Acid/pharmacology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 10
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    Response: seizures in drug-treated animals (1987)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1987-03-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Suzdak, P D -- Glowa, J R -- Crawley, J N -- Schwartz, R D -- Skolnick, P -- Paul, S M -- New York, N.Y. -- Science. 1987 Mar 6;235(4793):1127b-8b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17818967" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0036-8075
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