Influence of a number of diterpene alkaloids on the calcium homeostasis of rat cardiomyocytes. Structure-activity relationship

Sagdullaev, Botir T.; Abramov, AY; Gagel’gans, A. I.; Dzhakhangirov, F. N.; Usmanov, P. B.

doi:10.1007/bf02329600

Cited by 4 publications

(3 citation statements)

References 6 publications

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“…The effect of benzoylheteratisine (5) is achieved very rapidly, at the moment of the administration, but the du ration of its action is 1.5-2 h. 14,19, 20 It should be noted that all antiarrhythmic agents based on DTA are good antidotes for poisoning with lethal doses of aconitine and related alkaloids. This is an important problem because the poisoning in humans and animals with plants containing aconitine and related alkaloids still happens.…”

Section: Methodsmentioning

confidence: 99%

Antiarrhythmic agents based on diterpenoid alkaloids

Yunusov

2011

Russ Chem Bull

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Diterpenoid alkaloids comprise a large group of natural compounds produced by the plants of the genera Aconitum and Delphinium. Some of these compounds were found to manifest valuable pharmacological properties, including the unique antiarrhythmic activity. Allapinine (derived from the alkaloid lappaconitine) was approved as a drug. The investigation of the structure-activity relationship revealed structural elements responsible for the arrhythmogenic and antiarrhythmic properties.

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Section: Methodsmentioning

confidence: 99%

Antiarrhythmic agents based on diterpenoid alkaloids

Yunusov

2011

Russ Chem Bull

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“…The therapeutic potential of SON has been implicated in several applications including cardiac arrhythmia, inflammatory diseases, and wound healing [ 3 , 5 ]. The diverse peripheral effects of SON may imply a wide range of cellular targets and mechanisms including the induction of nuclear factor-erythroid factor 2-related factor 2 (Nrf2) and the inhibition of membrane Ca 2+ channels, growth factor receptors, and cytokine expression [ 6 , 7 , 8 , 9 ]. Pharmacokinetic studies have confirmed that systemically applied SON rapidly distributes in body tissues, and passes the blood–brain barrier resulting in a well-detectable level of the drug in the CNS [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Aconitum Alkaloid Songorine Exerts Potent Gamma-Aminobutyric Acid-A Receptor Agonist Action In Vivo and Effectively Decreases Anxiety without Adverse Sedative or Psychomotor Effects in the Rat

et al. 2022

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Songorine (SON) is a diterpenoid alkaloid from Aconitum plants. Preparations of Aconitum roots have been employed in traditional oriental herbal medicine, however, their mechanisms of action are still unclear. Since GABA-receptors are possible brain targets of SON, we investigated which subtypes of GABA-receptors contribute to the effects of SON, and how SON affects anxiety-like trait behavior and psychomotor cognitive performance of rats. First, we investigated the effects of microiontophoretically applied SON alone and combined with GABA-receptor agents picrotoxin and saclofen on neuronal firing activity in various brain areas. Next, putative anxiolytic effects of SON (1.0–3.0 mg/kg) were tested against the GABA-receptor positive allosteric modulator reference compound diazepam (1.0–5.0 mg/kg) in the elevated zero maze (EOM). Furthermore, basic cognitive effects were assessed in a rodent version of the psychomotor vigilance task (PVT). Local application of SON predominantly inhibited the firing activity of neurons. This inhibitory effect of SON was successfully blocked by GABA(A)-receptor antagonist picrotoxin but not by GABA(B)-receptor antagonist saclofen. Similar to GABA(A)-receptor positive allosteric modulator diazepam, SON increased the time spent by animals in the open quadrants of the EOM without any signs of adverse psychomotor and cognitive effects observed in the PVT. We showed that, under in vivo conditions, SON acts as a potent GABA(A)-receptor agonist and effectively decreases anxiety without observable side effects. The present findings facilitate the deeper understanding of the mechanism of action and the widespread pharmacological use of diterpene alkaloids in various CNS indications.

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“…The therapeutic potential of SON was implicated in several indications including cardiac arrhythmia, inflammatory diseases, and wound healing [3,5]. The diverse peripheral effects of SON may imply a wide range of its cellular targets and mechanisms including the induction of nuclear factor-erythroid factor 2-related factor 2 (Nrf2), and the inhibition of membrane Ca 2+ channels, growth factor receptors and cytokine expression [6][7][8][9]. Pharmacokinetic studies confirmed that systemically applied SON rapidly distributes in body tissues, and passes the blood-brain barrier resulting in a welldetectable level of the drug in the CNS [10,11].…”

Section: Introductionmentioning

confidence: 99%

<i>Aconitum</i> Alkaloid Songorine Exerts Potent Gamma-aminobutyric Acid A Receptor Agonist Action In Vivo and Effectively Decreases Anxiety Without Adverse Sedative or Psychomotor Effects in the Rat

Bali¹,

Bruszt²,

Köszegi³

et al. 2022

Preprint

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Songorine (SON) is a diterpenoid alkaloid from Aconitum plants. Preparations of Aconitum roots have been employed in traditional oriental herbal medicine, however, their mechanisms of action are still unclear. Since GABA-receptors are possible brain targets of SON, we investigated which subtypes of GABA-receptors contribute to the effects of SON, and how SON affects anxiety-like trait behavior and psychomotor cognitive performance of rats. First, we investigated the effects of microiontophoretically applied SON alone and combined with GABA-receptor agents picrotoxin and saclofen on neuronal firing activity in various brain areas. Next, putative anxiolytic effects of SON (1.0-3.0 mg/kg) were tested against the GABA-receptor positive allosteric modulator refer-ence compound diazepam (1.0-5.0 mg/kg) in the elevated zero maze (EOM). Furthermore, basic cognitive effects were assessed in a rodent version of the psychomotor vigilance task (PVT). Local application of SON predominantly inhibited the firing activity of neurons. This inhibitory effect of SON was successfully blocked by GABA(A)-receptor antagonist picrotoxin but not by GABA(B)-receptor antagonist saclofen. Similar to GABA(A)-receptor positive allosteric modulator diazepam, SON increased the time spent by animals in the open quadrants of the EOM without any signs of adverse psychomotor and cognitive effects observed in the PVT. We showed that, under in vivo conditions SON acts as a potent GABA(A)-receptor agonist and effectively decreases anxiety without observable side effects. The present findings facilitate the deeper understanding of the mechanism of action and the widespread pharmacological use of diterpene alkaloids in various CNS indications.

show abstract

Influence of a number of diterpene alkaloids on the calcium homeostasis of rat cardiomyocytes. Structure-activity relationship

Cited by 4 publications

References 6 publications

Antiarrhythmic agents based on diterpenoid alkaloids

Antiarrhythmic agents based on diterpenoid alkaloids

Aconitum Alkaloid Songorine Exerts Potent Gamma-Aminobutyric Acid-A Receptor Agonist Action In Vivo and Effectively Decreases Anxiety without Adverse Sedative or Psychomotor Effects in the Rat

<i>Aconitum</i> Alkaloid Songorine Exerts Potent Gamma-aminobutyric Acid A Receptor Agonist Action In Vivo and Effectively Decreases Anxiety Without Adverse Sedative or Psychomotor Effects in the Rat

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