Biomaterial Database

Electrophysiological effects of the anticonvulsant remacemide hydrochloride and its metabolite ARL 12495AA on rat CA1 hippocampal neurons in vitro. 1997

S K Norris, and A E King

Department of Physiology, University of Leeds, U.K.

The electrophysiological actions of the putative anticonvulsants remacemide hydrochloride and its des-glycine metabolite ARL 12495AA were examined using whole-cell recordings from CA1 hippocampal neurons in adult rat brain in vitro. Remacemide hydrochloride (4-400 microM) and ARL 12495AA (4-400 microM) limited sustained high frequency repetitive firing (SRF) induced by application of long duration depolarizing current pulses (20-400 pA, 500 msec). This SRF limitation was concentration-dependent, and equipotent IC50 values of 66 and 60 microM were calculated for remacemide hydrochloride and ARL 12495AA, respectively. Examination of the spike configuration revealed that, over the same concentration range, each compound caused a concentration-related reduction of: (a) the action potential amplitude; and (b) the rate-of-rise. Remacemide hydrochloride or ARL 12495AA increased spike duration and decreased or eliminated the spike after-hyperpolarization. Possible mechanisms for these electrophysiological actions including modulation of sodium and/or potassium channel activity are considered. It is suggested that such multiple mechanisms, including inhibition of SRF may be relevant to the anticonvulsant properties of remacemide hydrochloride and its metabolite, ARL 12495AA. The activity of both compounds as modulators of neuronal excitability indicates that metabolic conversion of remacemide hydrochloride to ARL 12495AA could enhance the therapeutic efficacy of the former.

UI	MeSH Term	Description	Entries
D009474	Neurons	The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.	Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D010627	Phenethylamines	A group of compounds that are derivatives of beta- aminoethylbenzene which is structurally and pharmacologically related to amphetamine. (From Merck Index, 11th ed)	Phenylethylamines
D005260	Female		Females
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
D000081	Acetamides	Derivatives of acetamide that are used as solvents, as mild irritants, and in organic synthesis.
D000200	Action Potentials	Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli.	Spike Potentials,Nerve Impulses,Action Potential,Impulse, Nerve,Impulses, Nerve,Nerve Impulse,Potential, Action,Potential, Spike,Potentials, Action,Potentials, Spike,Spike Potential
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
D017208	Rats, Wistar	A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.	Wistar Rat,Rat, Wistar,Wistar Rats
D051381	Rats	The common name for the genus Rattus.	Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus