Biomaterial Database

Putative benzodiazepine partial agonists demonstrate receptor heterogeneity. 1996

S W Chen, and H A Chen, and M F Davies, and G H Loew

Molecular Research Institute, Palo Alto, CA 94304, USA. Shuwen@Purisina.Molres.Org

This study explored whether the behavioral heterogeneity of benzodiazepine receptor (BDZR) ligands is a consequence of multiple receptor subtypes or partial agonism. Putative partial agonists Ro16-6028, Ro23-1590, Ro23-0364, and abecarnil were compared with U78875, a mixed agonist-antagonist, and CGS8216, an inverse agonist, in five BDZR-mediated functions: hyperphagia, anxiolysis, sedation, hypothermia, and anticonvulsant activity. Only abecarnil was an agonist in all end points. Each of the other drugs exhibited qualitatively different responses at these end points. Specifically, Ro23-0364 produced no effect on body temperature, but was an agonist at other tests. Ro23-1590 had no effect on anxiolysis and hypothermia, but was an agonist at other tests. In contrast to other putative partial agonists, Ro16-6028 was found to be an antagonist in sedation and U78875 was an antagonist in hypothermia, but both were agonists at other end points. These qualitative differences in activity in the five behavioral end points studied cannot be explained by partial agonism at a single receptor and indicate that these ligands differentially activate multiple BDZR subtypes.

UI	MeSH Term	Description	Entries
D006963	Hyperphagia	Ingestion of a greater than optimal quantity of food.	Overeating,Polyphagia,Polyphagias
D006993	Hypnotics and Sedatives	Drugs used to induce drowsiness or sleep or to reduce psychological excitement or anxiety.	Hypnotic,Sedative,Sedative and Hypnotic,Sedatives,Hypnotic Effect,Hypnotic Effects,Hypnotics,Sedative Effect,Sedative Effects,Sedatives and Hypnotics,Effect, Hypnotic,Effect, Sedative,Effects, Hypnotic,Effects, Sedative,Hypnotic and Sedative
D008024	Ligands	A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)	Ligand
D008297	Male		Males
D009043	Motor Activity	Body movements of a human or an animal as a behavioral phenomenon.	Activities, Motor,Activity, Motor,Motor Activities
D010433	Pentylenetetrazole	A pharmaceutical agent that displays activity as a central nervous system and respiratory stimulant. It is considered a non-competitive GAMMA-AMINOBUTYRIC ACID antagonist. Pentylenetetrazole has been used experimentally to study seizure phenomenon and to identify pharmaceuticals that may control seizure susceptibility.	Leptazole,Pentamethylenetetrazole,Pentetrazole,Cardiazol,Corasol,Corazol,Corazole,Korazol,Korazole,Metrazol,Metrazole,Pentazol,Pentylenetetrazol
D001831	Body Temperature	The measure of the level of heat of a human or animal.	Organ Temperature,Body Temperatures,Organ Temperatures,Temperature, Body,Temperature, Organ,Temperatures, Body,Temperatures, Organ
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
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D000927	Anticonvulsants	Drugs used to prevent SEIZURES or reduce their severity.	Anticonvulsant,Anticonvulsant Drug,Anticonvulsive Agent,Anticonvulsive Drug,Antiepileptic,Antiepileptic Agent,Antiepileptic Agents,Antiepileptic Drug,Anticonvulsant Drugs,Anticonvulsive Agents,Anticonvulsive Drugs,Antiepileptic Drugs,Antiepileptics,Agent, Anticonvulsive,Agent, Antiepileptic,Agents, Anticonvulsive,Agents, Antiepileptic,Drug, Anticonvulsant,Drug, Anticonvulsive,Drug, Antiepileptic,Drugs, Anticonvulsant,Drugs, Anticonvulsive,Drugs, Antiepileptic