Biomaterial Database

Flunitrazepam and nordiazepam slowly released from silastic capsules induce physical dependence in rat. 1995

X Jing, and E P Wala, and J W Sloan

Department of Anesthesiology, University of Kentucky, College of Medicine, Lexington 40536, USA.

The rates of in vitro release of flunitrazepam (FN), nordiazepam (ND) and diazepam (DZ) from silastic capsules were compared and found to be in the following order: DZ > FN > ND. Rats that were implanted subcutaneously with capsules filled with FN or ND for 5 to 7 weeks before administering flumazenil (FLU) (40 mg/kg, i.v.) showed precipitated abstinence as measured by the Precipitated Abstinence Score (PAS) which included a rapid onset of clonic and tonic-clonic convulsions. Rats implanted with DZ also demonstrated significant PAS and seizures. Implantation of similar doses of DZ, FN and ND resulted in different plasma levels of parent benzodiazepines and their metabolites that corresponded with their in vitro release: DZ > FN > ND. These data indicate that, as for DZ, the capsule implantation is an effective method of producing physical dependence on FN and ND in the rat.

UI	MeSH Term	Description	Entries
D003692	Delayed-Action Preparations	Dosage forms of a drug that act over a period of time by controlled-release processes or technology.	Controlled Release Formulation,Controlled-Release Formulation,Controlled-Release Preparation,Delayed-Action Preparation,Depot Preparation,Depot Preparations,Extended Release Formulation,Extended Release Preparation,Prolonged-Action Preparation,Prolonged-Action Preparations,Sustained Release Formulation,Sustained-Release Preparation,Sustained-Release Preparations,Timed-Release Preparation,Timed-Release Preparations,Controlled-Release Formulations,Controlled-Release Preparations,Extended Release Formulations,Extended Release Preparations,Slow Release Formulation,Sustained Release Formulations,Controlled Release Formulations,Controlled Release Preparation,Controlled Release Preparations,Delayed Action Preparation,Delayed Action Preparations,Formulation, Controlled Release,Formulations, Controlled Release,Prolonged Action Preparation,Release Formulation, Controlled,Release Formulations, Controlled,Sustained Release Preparation,Timed Release Preparation,Timed Release Preparations
D003708	Nordazepam	An intermediate in the metabolism of DIAZEPAM to OXAZEPAM. It may have actions similar to those of diazepam.	Dealkylprazepam,Demethyldiazepam,Deoxydemoxepam,Desmethyldiazepam,Nordiazepam,Calmday,N-Desalkylhalazepam,N-Descyclopropylmethyl-Prazepam,N-Descyclopropylmethylprazepam,N-Destrifluoroethylhalazepam,Nordaz,Norprazepam,Ro 5-2180,Tranxilium N,Vegesan,N Desalkylhalazepam,N Descyclopropylmethyl Prazepam,N Descyclopropylmethylprazepam,N Destrifluoroethylhalazepam,Ro 5 2180,Ro 52180
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
D004343	Drug Implants	Small containers or pellets of a solid drug implanted in the body to achieve sustained release of the drug.	Drug Implant,Drug Pellet,Pellets, Drug,Drug Pellets,Implant, Drug,Implants, Drug,Pellet, Drug
D005260	Female		Females
D005442	Flumazenil	A potent benzodiazepine receptor antagonist. Since it reverses the sedative and other actions of benzodiazepines, it has been suggested as an antidote to benzodiazepine overdoses.	Flumazepil,Anexate,Lanexat,Ro 15-1788,Romazicon,Ro 15 1788,Ro 151788
D005445	Flunitrazepam	A benzodiazepine with pharmacologic actions similar to those of DIAZEPAM that can cause ANTEROGRADE AMNESIA. Some reports indicate that it is used as a date rape drug and suggest that it may precipitate violent behavior. The United States Government has banned the importation of this drug.	Fluridrazepam,Rohypnol,Fluni 1A Pharma,Flunibeta,Flunimerck,Fluninoc,Flunitrazepam-Neuraxpharm,Flunitrazepam-Ratiopharm,Flunitrazepam-Teva,Flunizep Von Ct,Narcozep,RO-5-4200,Rohipnol,Flunitrazepam Neuraxpharm,Flunitrazepam Ratiopharm,Flunitrazepam Teva,RO54200,Von Ct, Flunizep
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
D000931	Antidotes	Agents counteracting or neutralizing the action of POISONS.	Antidote,Theriacs
D001682	Biological Availability	The extent to which the active ingredient of a drug dosage form becomes available at the site of drug action or in a biological medium believed to reflect accessibility to a site of action.	Availability Equivalency,Bioavailability,Physiologic Availability,Availability, Biologic,Availability, Biological,Availability, Physiologic,Biologic Availability,Availabilities, Biologic,Availabilities, Biological,Availabilities, Physiologic,Availability Equivalencies,Bioavailabilities,Biologic Availabilities,Biological Availabilities,Equivalencies, Availability,Equivalency, Availability,Physiologic Availabilities