a semirigid molecular probe for different ion channels or receptors. A ligand with activating effect on Cl^- channels and blocking effect on K⁺‚ Na⁺ and Ca²⁺ channels. Potent antiarrhythmic.
Represents a new class of anti-histaminic (non H1 or H2) anti-allergic drugs: potential antagonist of H-3 histamine and (non 5-HT-2) serotonine receptors. Diamine oxidase activator. Inhibits gastric secretion.

Quinuclidine derivative‚ C₂₀H₂₃NO.HCl ‚ synthetic.

For detailed information see the attached tables and abstracts.

Ion channels agent.

On Na⁺ channels (CA1-CA3 region of rat hippocampus neurons)‚ 5x10^-4 M results in 100 % blocking effect‚ 5x10-5 M in 50%.

On isolated throat ganglia neurons of the snail Limnea stagnalis (patch-clamp whole-cell recording):

* On K⁺ channels‚ irreversible blockade

-slow currents:10^-5 M results in 100% blocking effect and 10^-6 M in 40%

-fast currents:10^-5 M results in 55% blocking effect.

* On Ca²⁺ channels:10^-6 M results in 60% inhibition of conductivity.

* On Cl^- channels: 10^-7M results in 170% increase in conductivity.


Anti-allergic.

Non-sedative low anti-cholinergic anti-histaminic drug. Activity: guinea pig ileum‚ ED₅₀ = 5x10^-9 g/ml‚ pA₂ =5.3 (duration of action: 1.5 hours) [1-2]. Non-typical H-blocker (potentially H-3). Low binding to H-1 receptors: competition with [3H] Mepyramine at rat cortex H-1‚ IC₅₀ = 320 nM‚ pIC₅₀ = 76 for Diphenhydramine; no binding to H-2 receptors‚ or to 5HT-2 receptors [3].


Low affinity to M-AChR.

pIC50 [3H]-quinuclidinyl-3-benzylate‚ rat-brain (M-1)/heart(M-2) 6.36/5.23; guinea pig ileum 6.5 (methylfurmethide)‚ 6.2 (ACh); Pridinol 7.3/6.8‚ Atropine 9.0/10.0.


Anti-secretory.

Moderately suppresses gastric secretion‚ the effect is blocked by DAO inhibitor aminoguanidin [4].


Anti-AChE activityin vitro (human erythrocytes) Ki. 10⁴ = 2.33‚ type of inhibition: competitive.


DAO activator. 50 mg/kg p.o.‚ rat lung‚ 45 min. +33%‚ 60 min. + 45%‚ 180 min. +33% [5].


Extremely efficient anti-arrhythmic. Stops and prevents CaCl₂‚ Strofantin and Adrenaline arrhythmias: rabbits‚ 5 mg/kg: 100 % in 10-15 seconds; no effect on Aconitine arrhythmia (probably does not bind to site 2 of Na⁺ channels). Used in emergency clinical practice.


No influence on ECG‚ pace rate‚ no cardiodepressive effect [6].

Good penetration of biological membranes.

Low influence on the electrical activity of the brain [2].

1. Mashkovsky M.D. et al., "Further developments in research on the chemistry and pharmacology of synthetic quinuclidine derivatives." Progr. Drug. Res., 27:9-61
2. Kaminka M.E. et al., Farm. Toksikol (1977). (2):158-162
3. Kaminka M.E. et al., Farm. Toksikol (1988) (Russian). (2): 21-26
4. Gankina E.M. et al., Eksp. Klin. Farmacol. (1993) (Russian). (1):22-24
5. Kaminka M.E. et al., Bull Exp. Biol. Med. (1993) (Russian). (5):44-46
6. Baumanis E.A. et al., Farm. Toksikol (1980) (Russian). (1):36-41
7. Yakovlev G.M. et al., Farm. Toksikol (1991) (Russian). (5):25-27
8. Tondeur R. et al., Chim. Ther. (1966). 207
9. Villany et F.J. al., J. Med. Chem. (1975). 18(7):666-669