Biomaterial Database

The depressant effect of GYKI 52466 on spinal reflex transmission in rats is mediated via non-NMDA and benzodiazepine receptors. 1994

F Block, and M Schwarz

Department of Neurology, University of Essen, Germany.

The present study examined the mechanisms by which GYKI 52466 (1-(amino-phenyl)-4-methyl-7,8-methyldioxy-5H-2,3-benzodiazepine) exerts its muscle relaxant effects. Intrathecal injection of the specific N-methyl-D-aspartate (NMDA) receptor antagonist (-)-2-amino-7-phosphonoheptanoate (AP7, 50-500 nmol) and systemic application of the benzodiazepine diazepam (0.2-5 mg/kg) dose dependently reduced the integrated area of the polysynaptic flexor reflex without affecting the monoxynaptic H-reflex. In contrast, intrathecal administration of the non-NMDA receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX, 0.1-10 nmol) depressed the H-reflex in a dose-dependent manner without affecting the flexor reflex. The depressant effect of GYKI 52466 on the flexor reflex was reduced by coadministration with flumazenil (5 mg/kg i.p.), an antagonist at the benzodiazepine receptor, whereas coadministration of the non-NMDA receptor agonist alpha-amino-3-hydroxy-5-tertbutyl-4-isoxazole-propionic acid (ATPA, 0.1 pmol) with GYKI 52466 attenuated the reduction of the H-reflex induced by GYKI 52466. The chosen doses of flumazenil and ATPA did not affect spinal reflex transmission when given alone. These data suggest that GYKI 52466 depresses spinal reflex transmission via an action on non-NMDA receptors and on benzodiazepine receptors.

UI	MeSH Term	Description	Entries
D007278	Injections, Spinal	Introduction of therapeutic agents into the spinal region using a needle and syringe.	Injections, Intraspinal,Injections, Intrathecal,Intraspinal Injections,Intrathecal Injections,Spinal Injections,Injection, Intraspinal,Injection, Intrathecal,Injection, Spinal,Intraspinal Injection,Intrathecal Injection,Spinal Injection
D008297	Male		Males
D009435	Synaptic Transmission	The communication from a NEURON to a target (neuron, muscle, or secretory cell) across a SYNAPSE. In chemical synaptic transmission, the presynaptic neuron releases a NEUROTRANSMITTER that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across ELECTRICAL SYNAPSES.	Neural Transmission,Neurotransmission,Transmission, Neural,Transmission, Synaptic
D011810	Quinoxalines		Quinoxaline
D011963	Receptors, GABA-A	Cell surface proteins which bind GAMMA-AMINOBUTYRIC ACID and contain an integral membrane chloride channel. Each receptor is assembled as a pentamer from a pool of at least 19 different possible subunits. The receptors belong to a superfamily that share a common CYSTEINE loop.	Benzodiazepine-Gaba Receptors,GABA-A Receptors,Receptors, Benzodiazepine,Receptors, Benzodiazepine-GABA,Receptors, Diazepam,Receptors, GABA-Benzodiazepine,Receptors, Muscimol,Benzodiazepine Receptor,Benzodiazepine Receptors,Benzodiazepine-GABA Receptor,Diazepam Receptor,Diazepam Receptors,GABA(A) Receptor,GABA-A Receptor,GABA-A Receptor alpha Subunit,GABA-A Receptor beta Subunit,GABA-A Receptor delta Subunit,GABA-A Receptor epsilon Subunit,GABA-A Receptor gamma Subunit,GABA-A Receptor rho Subunit,GABA-Benzodiazepine Receptor,GABA-Benzodiazepine Receptors,Muscimol Receptor,Muscimol Receptors,delta Subunit, GABA-A Receptor,epsilon Subunit, GABA-A Receptor,gamma-Aminobutyric Acid Subtype A Receptors,Benzodiazepine GABA Receptor,Benzodiazepine Gaba Receptors,GABA A Receptor,GABA A Receptor alpha Subunit,GABA A Receptor beta Subunit,GABA A Receptor delta Subunit,GABA A Receptor epsilon Subunit,GABA A Receptor gamma Subunit,GABA A Receptor rho Subunit,GABA A Receptors,GABA Benzodiazepine Receptor,GABA Benzodiazepine Receptors,Receptor, Benzodiazepine,Receptor, Benzodiazepine-GABA,Receptor, Diazepam,Receptor, GABA-A,Receptor, GABA-Benzodiazepine,Receptor, Muscimol,Receptors, Benzodiazepine GABA,Receptors, GABA A,Receptors, GABA Benzodiazepine,delta Subunit, GABA A Receptor,epsilon Subunit, GABA A Receptor,gamma Aminobutyric Acid Subtype A Receptors
D012018	Reflex	An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord.
D003864	Depression, Chemical	The decrease in a measurable parameter of a PHYSIOLOGICAL PROCESS, including cellular, microbial, and plant; immunological, cardiovascular, respiratory, reproductive, urinary, digestive, neural, musculoskeletal, ocular, and skin physiological processes; or METABOLIC PROCESS, including enzymatic and other pharmacological processes, by a drug or other chemical.	Chemical Depression,Chemical Depressions,Depressions, Chemical
D003975	Diazepam	A benzodiazepine with anticonvulsant, anxiolytic, sedative, muscle relaxant, and amnesic properties and a long duration of action. Its actions are mediated by enhancement of GAMMA-AMINOBUTYRIC ACID activity.	7-Chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one,Apaurin,Diazemuls,Faustan,Relanium,Seduxen,Sibazon,Stesolid,Valium
D004305	Dose-Response Relationship, Drug	The relationship between the dose of an administered drug and the response of the organism to the drug.	Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004558	Electric Stimulation	Use of electric potential or currents to elicit biological responses.	Stimulation, Electric,Electrical Stimulation,Electric Stimulations,Electrical Stimulations,Stimulation, Electrical,Stimulations, Electric,Stimulations, Electrical