Талатисамин

Description

Talatisamine is a diterpene alkaloid of the aconitane series, belonging to the dolphin type. Isolated from plants of the genus Aconitum, in particular from Aconitum thalassicum; also recorded in Aconitum piepunense and Aconitum legendrei. Alkaloids of this group are contained in raw materials known in folk medicine as tsaou. Systematically, the compound is described as (1α,14α,16β)-20-ethyl-1,16-dimethoxy-4-(methoxymethyl)aconitane-8,14-diol.

Basic Attributes

• CAS No: 20501-56-8
• Chemical formula: C24H39NO5
• Molecular weight: 421.574
• Exact weight: 421.57
• PSA Specifications: 71.39000
• XLogP3: −0.50

Physico-chemical properties

• Density: 1.3 ± 0.1 g/cm³
• Melting point: 138–140 °C
• Boiling point: 533.9 ± 50.0 °C at 760 mm Hg. Art.
• Flash point: 276.7 ± 30.1 °C
• Refractive index: 1.588

The negative value of XLogP3 (−0.50) with a polar surface of 71.4 shows that the molecule is hydrophilic: three methoxy groups and two hydroxyl groups with a relatively compact polycyclic framework keep it in the aqueous phase. This distinguishes talatisamine from most lipophilic diterpene alkaloids and is taken into account when choosing a dissolution medium.

Biological activity

Talatisamine has been identified as a specific blocker of delayed rectifier potassium channels. Experimental characteristics obtained on rat hippocampal neurons:

• external application of the substance reversibly suppresses the delayed rectifying current IK with an IC50 value of 146.0 ± 5.8 μM, the effect is voltage-dependent
• the effect on voltage-controlled sodium and calcium currents is extremely weak even at concentrations of 1–3 mM, that is, selectivity is pronounced
• causes a significant hyperpolarizing shift in steady-state channel activation
• does not affect the stationary inactivation of IK and the restoration of the channel from the inactivated state

From the last two observations, a conclusion about the mechanism follows: there is no allosteric effect on the channel, thalatisamine works as a pure blocker that binds to the external entrance of the pore. Separately, the compound was shown to reduce amyloid beta Aβ(1-40)-induced increases in IK current and cytotoxicity in primary cortical neurons. Inhibition of potassium efflux by IK channel blockade is being considered as a potentially useful avenue for the treatment of Alzheimer's disease, and thalatisamine is being discussed as a lead compound for further study. The substance has also been reported to have hypotensive and antiarrhythmic activity.

Scope of application

• Electrophysiology reagent: a selective tool for switching off delayed rectifying current
• analytical standard for the determination of diterpene alkaloids in raw materials of the genus Aconitum
• object of neuropharmacological research

Storage and handling

The harmonized GHS classification, transport codes, labels, hazard class codes and toxicity data are not given in the card - this information is taken from the batch’s safety data sheet. Alkaloids of the genus Aconitum belong to potent compounds, so handling is carried out with limited access and separate accounting: work under a hood, gloves, safety glasses, separate waste collection. Store in a tightly closed container, protect from light and heat.