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Abstract

Forty-three bisammonium ganglionic blockers were synthesized to study the structure of the ion channel of nicotinic acetylcholine receptor. The conformational parameters of these blockers were studied, and their effects toward the ganglionic transmission in situ on the sympathetic feline upper cervical ganglions and in vitro on the parasympathetic guinea-pig small intestine ganglions were determined. A model of the binding site for the bisammonium ganglionic blockers in the neuronal ion channel was proposed.

Combined blockade of AMPA and NMDA receptors in the brain of rats prevents pentylenetetrazole-induced clonic and tonic-clonic seizures without ataxia

“…Pentylenetetrazole in a toxic dose of 70 mg/kg was injected intramuscularly to induce seizures [2]. Local clonic seizures (forelimb or hindlimb clonus) and generalized tonic-clonic seizures in rats (clonic seizures and tonic hindlimb extension) were recorded over 30 min after pentylenetetrazole injection.…”

“…Pentylenetetrazole-induced seizures in rats are associated with glutamate activation of AMPA and NMDA receptors in the brain [5,6,14]. NMDA receptor blockade with MK-801, memantine, and arcaine significantly decreases the severity of generalized tonic-clonic seizures [2,3,14], but has no effect on pentylenetetrazole-induced local clonic seizures in rats [12,14]. Another disadvantage of NMDA receptor antagonists is low therapeutic index.…”

“…Another disadvantage of NMDA receptor antagonists is low therapeutic index. Ataxia and stereotypy in rats are observed after treatment with these drugs in doses, which exceed the effective anticonvulsant dose only by several times [2,3,13].Combined administration of NMDA and AMPA receptor antagonists in low doses prevents not only tonic-clonic seizures, but also kindled clonic seizures. This treatment causes no side effects, which are usually observed after separate administration of NMDA and AMPA receptor antagonists in high doses [7,9,11].…”

“…Another disadvantage of NMDA receptor antagonists is low therapeutic index. Ataxia and stereotypy in rats are observed after treatment with these drugs in doses, which exceed the effective anticonvulsant dose only by several times [2,3,13].…”

Effect of modulators of the polyamine site on the development of seizures induced by systemic and intracerebral administration of N-methyl-D-aspartate in albino mice

“…Address for correspondence: g2119@ online.ru. V. E. GmiroAntagonists of the polyamine site of N-methyl-Daspartate (NMDA) receptors arcaine and ifenprodil in systemic administration are not inferior to NMDA receptor channel blockers memantine and MK-801 by their anticonvulsant activity in seizures modeled by systemic administration of NMDA and pentylenetetrazole and depending on permeability of the blood-brain barrier (BBB) [1,2,7,12].However, systemic administration of polyamine antagonists, in contrast to MK-801 and memantine, is low effective during electric shock-induced or audiogenic seizures, which do not depend on BBB permeability [5,6]. Since polyamine antagonists after peripheral administration decrease BBB permeability [4,9], it can be expected that intraperitoneal injection of arcaine would reduce the severity of seizures induced by intraperitoneal injection of NMDA due to a decrease in BBB permeability for NMDA, but will not modulate the severity of seizures induced by intracerebral administration of NMDA not depending on BBB permeability.…”