Effects of Anticonvulsant Drugs on Nerve Terminals

Abstract

SUMMARY The anticonvulsant agents diphenyrhydantoin(DPH) and diphenylthiohydantoin (DPTH) suppress repetitive after‐discharges originating in the motor nerve endings of the cat soleus nerve. Since these repetitive after‐discharges are responsible for virtually all of the posttetanic potentiation in this neuromuscular junction, DPH, DPTH and to a lesser degree certain other anticonvulsants reduce PTP. The repetitive after‐discharge seems to arise by a process of intra‐neuronal potential difference leading to high‐frequency firing, a process postulated to play a role in epileptogenic focal firing. The capacity of DPH to suppress hyperpolarization of nerve endings subjected to high‐frequency stimulation probably accounts for DPH's efficacy in suppressing repetitive after‐discharges and its previously described capacity to suppress posttetanic potentiation in spinal cord monosynaptic pathways. RÉSUMÉ Les médicaments anticonvulsifsdiphénylhydantoïne (DPH)etdiphénylthiohydantoïne (DPTH) suppriment les post‐décharges répétitives qui se produisent dans les termi‐naisons du nerf soleus du chat. Puisque ces post‐décharges répétitives sont respon‐sables de presque toute la potentiation post‐tétanique (PPT) dans cette jonction neuro‐musculaire, DPH, DPTH et à un moindre degré certains autres médicaments anti‐convulsifs font diminuer la PPT. La post‐décharge répétitive semble se produire par une différence de potentiel intra‐neuronale qui est àľorigine ďune décharge de haute fréquence, un processus qui jouerait un rôle dans la décharge ďun foyer épileptogène. La capacityé de DPH de supprimer ľhyperpolarisation des terminaisons neuronales soumises à une stimulation à haute fréquence explique probablement ľefficacité de DPH de supprimer des post‐décharges répétitives et sa capacityé de supprimer la PPT dans le trajet monosynaptique spinal qui a déjàété décrite.

Neuroexcitatory and Depressant Effects of Penicillin at the Cat Soleus Neuromuscular Junction

“…The mechanism for the induction of repetitive potentials in motor nerve endings produced by anticholinesterases (Hubbard, 1965) or posttetanically is believed to be the augmentation (Standaert and Riker, 1967;Raines and Standaert, 1969) and prolongation of the negative afterpotential of an action potential evoked in the nerve terminals. The prolonged negative afterpotential is believed to act as a constant current sink which induces the contiguous axon to fire repetitively.…”

Effects of Phenytoin on the Cyclic Nucleotide System in the Motor Nerve Terminal

“…In this preparation PTP is thought to be caused by stimulus bound PTR activity in the motor nerve terminal, which occurs because nerves are hyperpolarized after high frequency stimulation. Phenytoin is thought t o depress PTR by reducing this after-hyperpolarization (Raines and Standaert, 1969). The question arises a s to how depression of post-tetanic hyperpolarization is accomplished.…”

“…Phenytoin has been reported to depress each of these phenomena. It has been shown t o stabilize the membrane against depolarizing influences (Korey, 1951: Lipicky et al, 1972 and to depress the afterhyperpolarization a n d prolonged negative after-potentials which follow a period of high frequency stimulation of nerve endings (Raines and Standaert, 1969;Ayala et al, 19776). Phenytoin also has been reported to depress neurotransmitter release from cholinergic (Su and Feldman, 1973;Pincus, 1977) as well as adrener-gic (Pincus and So0 Hee Lee, 1973) nerve terminals.…”

Concurrent medication and the neuromuscular junction

“…There have been reports showing a post‐junctional effect, a prejunctional effect and a reduction in synthesis of ACh [52]. Phenytoin also has a stabilizing effect on neuronal membranes related to its action on the transÍcellular flux of sodium, potassium and calcium ions [53]. Decreased sensitivity to metocurine during long‐term phenytoin therapy may also be attributable to altered protein binding and ACh receptor changes [54].…”