Synthesis and physiological activity of some adamantane derivatives

Fridman, A. L.; Zalesov, V. S.; Kon'shina, L. O.; Kolobov, N. A.; Dolbilkin, K. V.; Моисеев, И. К.; Mratkhuzina, T. A.; Belyaev, P. G.

doi:10.1007/bf00757834

Cited by 4 publications

(4 citation statements)

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“…In the present study, AdCA did not show any anti-seizure effect against tonic seizures induced by MES, even at the highest sedative dose (300 mg/kg). This observation is in contrast to the report of Fridman et al [3] who reported 300 mg/kg of ED50 value for AdCA in MES test.…”

Section: Discussioncontrasting

confidence: 99%

“…Nevertheless, AdCA itself also possesses pharmacologic activity. It has previously been reported that AdCA has anticonvulsant activity [3] . Moreover, it is a potent and specific inhibitor of the enzyme, ceramide kinase, and can, therefore, control the cell signaling [15] .…”

Section: Discussionmentioning

confidence: 98%

“…We examined the effect of non-sedative doses of AdCA but did not find any anticonvulsant activity [2] . However, in the report of Fridman et al [3] , it has not mentioned whether any sedative effect is detected at the anticonvulsant doses. Meanwhile, AdCA has been a molecule of interest for medicinal chemists in the last 50 years and widely used for the improvement of the pharmacodynamics and pharmacokinetics of drugs and biologically active compounds [4] .…”

Section: Introductionmentioning

confidence: 95%

“…However, there is an old short report that indicates the anticonvulsant activity of AdCA in MES and PTZ models after i.p. administration to mice [3] . We examined the effect of non-sedative doses of AdCA but did not find any anticonvulsant activity [2] .…”

Section: Introductionmentioning

confidence: 99%

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Anti-Seizure Activity of 1-Adamantane Carboxylic Acid in Common Experimental Seizure Models: Role of Benzodiazepine-GABAA Receptors

Ghanbari

Gavzan

Khoshkroodian

et al. 2021

ibj

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Background: Despite introduction of modern antiepileptic drugs, 30% of epileptic patients are still drug resistant. Remarkable three-dimensional spatial structure of AdCA, yet the simplicity of the molecule, makes AdCA a promising lead compound. Methods: Sedative/motor impairment and 24-h mortality rate of AdCA were determined in mice. Impact of AdCA on (1) threshold and occurrence of clonic seizures induced by PTZ in mice, (2) incidence of tonic seizures induced by MES in mice, and (3) incidence of generalized seizures and duration of evoked afterdischarges in amygdala-kindled rats, were determined. The role of benzodiazepine receptors in the AdCA effect on clonic seizure threshold was also assessed. Results: AdCA showed sedative effect (TD50 = 224.5 [190.2-289.9] mg/kg). LD50 = 805.5 (715.2-988.1) mg/kg was obtained for AdCA. The compound increased PTZ seizure threshold from 180 mg/kg (p < 0.05) and also inhibited the incidence of clonic seizures (ED50 = 256.3 [107.4-417.3] mg/kg). AdCA also decreased afterdischarge duration (p < 0.01) and the incidence of generalized seizures (ED50 < 50 mg/kg) in the kindled rats. However, AdCA did not protect mice against tonic seizures induced by MES. The benzodiazepine receptor antagonist flumazenil prevented the increase of seizure threshold by AdCA. Conclusion:AdCA possesses anticonvulsant activity in kindling and PTZ models through the activation of benzodiazepine/GABAA receptors with acceptable therapeutic index.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 98%