Effects of Verapamil and Amiodarone on Sympathoadrenal System and Balance of Excitatory and Inhibitory Amino Acids in Rat Medulla Oblongata

Abstract

Local injection of verapamil into ventrolateral region of the medulla oblongata triggered the release of epinephrine. Verapamil increased the total content of norepinephrine and epinephrine by 560% and decreased the content of serotonin by 46%. Verapamil had no effect on norepinephrine/epinephrine and norepinephrine/(norepinephrine+epinephrine) ratios in normal rats. Blockade of K+-channels in the medulla oblongata by local injection of 0.001 mg amiodarone did not change the levels of epinephrine and norepinephrine and norepinephrine/epinephrine and norepinephrine/(norepinephrine+epinephrine) ratios. In the medulla oblongata, verapamil proportionally increased the levels of norepinephrine, dopamine, and L-DOPA. Similarly, amiodarone increased the levels of L-DOPA and dopamine by 2.6 and 3.2 times, respectively. Amiodarone shifted the ratio of neuroactive amino acids towards inhibitory transmitters.

Anticonvulsant and hypnotic effects of amiodarone

“…This drug is highly lipid-soluble, and had been shown to pass into the brain (Wyss et al, 1990;Riva et al, 1982) and also to increase the concentrations of GABA and glycine (Turovaya et al, 2005); thus we may speculate that this drug had shown synergic effect with pentobarbital. Ohtsuka et al(2006) reported that barbiturates used as anticonvulsant drug at high concentrations but not at clinically relevant concentrations inhibited ATP-sensitive K + channel (K ATP ) channels activated by intracellular ATP depletion in rat substantia nigra, and Holmes et al(2000) reported that amiodarone inhibited the K ATP channels.…”

“…Following PTZ-induced seizures, Takemiya et al(2003) showed that COX-2 had induced prostaglandins and had enhanced levels of prostaglandin D 2 and prostaglandin E 2 . In addition, Turovaya et al(2005) reported that amiodarone had increased the concentrations of inhibitory GABA and glycine and had decreased those of excitatory aspartate and glutamate in rat medulla oblongata. In our study, the anticonvulsant effect of amiodarone in PTZ-induced seizures may be partially due to blockage of ion channels (Na + , K + and Ca 2+ )…”

“…However, studies related with its central nervous system (CNS) effects are still limited. Only one study reported that it increased the concentrations of γ-aminobutyric acid (GABA) and glycine and decreased those of aspartate and glutamate in rat medulla oblongata (Turovaya et al, 2005).…”

Amiodarone-associated Optic Neuropathy—A Clinical Criteria–based Diagnosis?

“…[6][7][8][9][10][11][12][13][14][15][16][17][18] One pathophysiologic theory of damage is mechanical or biochemical decrease of axoplasmic flow due to deposition of lamellar bodies within optic nerve axons. 3 Experimental studies suggest potential neurotoxic effect of amiodarone, [19][20][21][22][23] and in 2016, a novel potential pathomechanism was reported by Liao et al 24 This study showed that amiodarone induced apoptosis of RGC-5 cells (a clonal, retinal, neuronal cell line, established as a model to study glaucomatous damage in vitro) via inhibiting the phosphoinositide 3-kinase (PI3K)/Akt/FoxO3a pathway. However, overall, it is still controversial whether amiodarone-associated optic neuropathy (AAON) is a mere drug related condition or whether it represents a form of non-arteritic ischaemic neuropathy (NAION) in a high-risk cardiovascular population.…”

Amiodarone-associated optic neuropathy in the treatment of cardiovascular diseases

“…В результате экспериментальных исследований установлено, что токсичность амиодарона обусловлена блокированием Na + , K + или Ca 2+ -каналов [25] с последующим увеличением уровней L-допа и допамина, что приводит к изменению соотношения нейроактивных аминокислот и ингибиторных трансмиттеров [26]. Нейротоксичность возникает вследствие ингибирования активности протеинкиназы С и кальмодулин-регулирующих ферментов, модулирующих вне-и внутриклеточные сигналы через мембрану нейронов [27].…”