Aconitum and delphinium diterpenoid alkaloids of local anesthetic activity: comparative QSAR analysis based on GA-MLRA/PLS and optimal descriptors approach.

The duration of anesthesia (related to protein binding of a drug) and the onset time (determined by the pKa) are important characteristics in assessment of local anesthetic agents. They are known to be affected by a number of factors. Early studies of antiarrhythmic diterpenoid alkaloids from plants Aconitum and Delphinium suggested that they possess local anesthetic activity due to their ability to suppress sodium currents of excited membranes.

Aconitum and Delphinium alkaloids of curare-like activity. QSAR analysis and molecular docking of alkaloids into AChBP.

Early studies have shown that some of diterpenoid alkaloids, found in highly toxic plants of the genera Aconitum and Delphinium, act at neuronal nicotinic acetylcholine receptors (nAChRs) and exhibit potent N-cholinolytic activity. In the current study, GA-MLRA and GA-PLS approaches have been used to build QSAR models to predict N-cholinolytic activity measured in vivo (blockade of neuromuscular conductivity, BNMC and third eyelid relaxing activity, TYRA) and in vitro (suppression of frog's abdominal straight muscles on acetylcholine, SAM) for a series of diterpenoid alkaloids. Random splitting of a data set (five trials in total) produced QSAR models of a good level of correlation between experimental in vitro/in vivo and calculated N-cholinolytic activity expressed as log(1/ED(50)) with following average statistical parameters: log BNMC (r(2) = 0.

Aconitum and Delphinium alkaloids "Drug-likeness" descriptors related to toxic mode of action.

Large series of Aconitum and Delphinium alkaloids have been investigated by means of QSAR analysis. Descriptors related to "drug-likeness" of molecules were selected to discriminate between "drugs" and "non-drugs" amongst diterpenoid alkaloids of interest. A usefulness of such approach has been assessed and it proved to give reliable results on whether a particular diterpenoid alkaloid is likely to be either poison or drug.

[Antiarrhythmic drug allapinin: review of results of clinical investigation].

Antiarrhythmic drug allapinin has been used in clinical practice for a long time but data of investigation of its effects and mechanism of action are scanty. The aim of this review is to summarize results of clinical studies of allapinin supplementing them with personal unpublished data. The review embraces pharmacokinetics and pharmacodynamics of the drug, its efficacy in the treatment of various cardiac rhythm disturbances and side effects.

[Effects of allapinin on sodium currents in isolated neurons of the trigeminal ganglia and cardiomyocytes of rats].

Block of sodium currents by allapinin (diterpene alkaloid with strong antiarrhythmic properties) was investigated in isolated, voltage clamped rat trigeminal neurons and cultured neonatal rat single ventricular myocytes. Allapinin produces a decrease in sodium current amplitude without any changes in voltage dependent properties. Possible differences between the mechanisms of antiarrhythmic effect of diterpene alkaloids and classic antiarrhythmic agents have been analysed.