Carbamazepine pharmacokinetics-pharmacodynamics in genetically epilepsy-prone rats. 1999

J F Graumlich, and R G McLaughlin, and D Birkhahn, and N Shah, and A Burk, and P C Jobe, and J W Dailey
Department of Biomedical and Therapeutic Sciences and Medicine, University of Illinois, College of Medicine at Peoria, 61656, USA. jfg@uic.edu

Carbamazepine produces dose-related anticonvulsant effects in epilepsy models including the genetically epilepsy-prone rat (GEPR) model and the rat maximal electroshock model. Dose-response relationships are quantitatively different among the models. Against electroshock seizures in Sprague-Dawley rats the ED50 dose is 7.5 mg/kg whereas the ED50 against audiogenic seizures in severe seizure GEPRs (GEPR-9s) is 3 mg/kg. In contrast, the ED50 in moderate seizure GEPRs (GEPR-3s) is 25 mg/kg. The present study was designed to ascribe dose-response differences among the three rat strains to pharmacokinetic or pharmacodynamic factors. After systemic carbamazepine, pharmacokinetic studies revealed differences in area under the concentration-vs.-time curve. In other experiments, carbamazepine-induced serotonin release from hippocampus was used as a pharmacodynamic marker. In a concentration-controlled design using intracerebral microdialysis, hippocampal carbamazepine infusions produced similar concentration-response relations for the three rat strains. These data support the hypothesis that dose-response differences among the three rat strains are primarily pharmacokinetic in nature.

UI MeSH Term Description Entries
D007274 Injections, Intraperitoneal Forceful administration into the peritoneal cavity of liquid medication, nutrient, or other fluid through a hollow needle piercing the abdominal wall. Intraperitoneal Injections,Injection, Intraperitoneal,Intraperitoneal Injection
D002220 Carbamazepine A dibenzazepine that acts as a sodium channel blocker. It is used as an anticonvulsant for the treatment of grand mal and psychomotor or focal SEIZURES. It may also be used in the management of BIPOLAR DISORDER, and has analgesic properties. Amizepine,Carbamazepine Acetate,Carbamazepine Anhydrous,Carbamazepine Dihydrate,Carbamazepine Hydrochloride,Carbamazepine L-Tartrate (4:1),Carbamazepine Phosphate,Carbamazepine Sulfate (2:1),Carbazepin,Epitol,Finlepsin,Neurotol,Tegretol
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
D004827 Epilepsy A disorder characterized by recurrent episodes of paroxysmal brain dysfunction due to a sudden, disorderly, and excessive neuronal discharge. Epilepsy classification systems are generally based upon: (1) clinical features of the seizure episodes (e.g., motor seizure), (2) etiology (e.g., post-traumatic), (3) anatomic site of seizure origin (e.g., frontal lobe seizure), (4) tendency to spread to other structures in the brain, and (5) temporal patterns (e.g., nocturnal epilepsy). (From Adams et al., Principles of Neurology, 6th ed, p313) Aura,Awakening Epilepsy,Seizure Disorder,Epilepsy, Cryptogenic,Auras,Cryptogenic Epilepsies,Cryptogenic Epilepsy,Epilepsies,Epilepsies, Cryptogenic,Epilepsy, Awakening,Seizure Disorders
D006207 Half-Life The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. Halflife,Half Life,Half-Lifes,Halflifes
D006624 Hippocampus A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation. Ammon Horn,Cornu Ammonis,Hippocampal Formation,Subiculum,Ammon's Horn,Hippocampus Proper,Ammons Horn,Formation, Hippocampal,Formations, Hippocampal,Hippocampal Formations,Hippocampus Propers,Horn, Ammon,Horn, Ammon's,Proper, Hippocampus,Propers, Hippocampus,Subiculums
D000161 Acoustic Stimulation Use of sound to elicit a response in the nervous system. Auditory Stimulation,Stimulation, Acoustic,Stimulation, Auditory
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
D012701 Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator. 5-HT,5-Hydroxytryptamine,3-(2-Aminoethyl)-1H-indol-5-ol,Enteramine,Hippophaine,Hydroxytryptamine,5 Hydroxytryptamine

Related Publications

J F Graumlich, and R G McLaughlin, and D Birkhahn, and N Shah, and A Burk, and P C Jobe, and J W Dailey
May 1997, Neuroscience letters,
J F Graumlich, and R G McLaughlin, and D Birkhahn, and N Shah, and A Burk, and P C Jobe, and J W Dailey
June 1996, General pharmacology,
J F Graumlich, and R G McLaughlin, and D Birkhahn, and N Shah, and A Burk, and P C Jobe, and J W Dailey
October 1997, The Journal of pharmacy and pharmacology,
J F Graumlich, and R G McLaughlin, and D Birkhahn, and N Shah, and A Burk, and P C Jobe, and J W Dailey
December 2004, Neuropharmacology,
J F Graumlich, and R G McLaughlin, and D Birkhahn, and N Shah, and A Burk, and P C Jobe, and J W Dailey
February 2005, Comparative medicine,
J F Graumlich, and R G McLaughlin, and D Birkhahn, and N Shah, and A Burk, and P C Jobe, and J W Dailey
October 1992, Neurochemical research,
J F Graumlich, and R G McLaughlin, and D Birkhahn, and N Shah, and A Burk, and P C Jobe, and J W Dailey
January 1988, General pharmacology,
J F Graumlich, and R G McLaughlin, and D Birkhahn, and N Shah, and A Burk, and P C Jobe, and J W Dailey
July 1997, Naunyn-Schmiedeberg's archives of pharmacology,
J F Graumlich, and R G McLaughlin, and D Birkhahn, and N Shah, and A Burk, and P C Jobe, and J W Dailey
January 1989, Epilepsy research,
J F Graumlich, and R G McLaughlin, and D Birkhahn, and N Shah, and A Burk, and P C Jobe, and J W Dailey
January 1991, Epilepsy research. Supplement,
Copied contents to your clipboard!