Effects of piperazine derivatives on the activity of frog skeletal muscle fibers.
1. This study was undertaken to characterize the effects of some piperazine derivatives on excitable cell membranes. Three original Bulgarian compounds with favorable effects on cardiovascular and nervous system--piperazine derivatives with code names P-11 (N1-[3-oxo-3-phenyl-2-methyl-propyl]-N4-[trans-3-hydroxy-1,2,3,4- tetrahydro-2-naphthyl]-piperazine dihydrochloride), AS2 (N1-benzhydryl-N4-allyl piperazine dihydrochloride) and 35-M (Schiff's base of N1-benzhydryl-N4-aminopiperazine with triacetonamine, dioxalate salt) were tested in experiments with conventional microelectrode technique on isolated frog muscle fibers. 2. After 30-min treatment with tested drugs at concentrations of 10-100 microM the recorded intra-(ICAP) and extracellular action potentials (ECAPs) showed an amplitude decrease and duration increase. The total ionic current (Ii) decreased as the outward phase was almost abolished by P-11. The propagation velocity (PV) of excitation and the twitch amplitude also decreased. These changes were agent- and concentration-dependent. 3. The effect potency of the agents diminished in the following order: P-11 > AS2 > 35-M. 4. Concentrations higher than 100 microM for all agents completely, but reversibly, inhibited membrane excitability. 5. The results demonstrate compound- and concentration-induced modulation of Ca2+ current with blockade of Ca(2+)-dependent K+ and Cl- membrane channels of muscle fiber treated with the compound tested.
Radicheva
N
N
Institute of Biophysics, Bulgarian Academy of Sciences, Sofia, Bulgaria.
Vydevska
M
M
Mileva
K
K
D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D000969:Antinematodal Agents / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D018482:Muscle, Skeletal / Q000187:drug effects*; D000077489:Piperazine; D010879:Piperazines / Q000494:pharmacology*; D011893:Rana esculenta
D000969:Antinematodal Agents; D010879:Piperazines; D000077489:Piperazine