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.

• Molecular Weight : 329.87 Da.
  
  
• Melting Point : 296-298 °C (decomp.).
  
  
• Solubility in : sparingly in water (25°C: 11.6 mM); better in 50% ethanol.
  
  
• Purity min. : min. 98 %.
  (TLC [on "Silufol UV-254", MeOH-NH3 (25%) 10:1, Rf = 0.16. Visualization by UV-light followed by Dragendorff's reagent], NMR[CD3OD]).
  
  
• Physical Form : colorless crystal powder.
  
  
• Chemical Name : (3-quinuclidinyl)diphenyl carbinol hydrochloride, (3-quinuclidinyl)diphenyl methanol hydrochloride.
  
  
• Biological Activity : 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].
  
  
• Toxicity (LD₅₀) : mice (orally): 360 mg/kg.
  mice (i.v.): 62 mg/kg
  
  
• Storage recommendations : Stable in dry state and in solution up to 100 °C. Dissolves slowly, use heating or boiling. Solution for use: dissolve in water: 10^-3 M (2 mg in 6.06 ml).
  
  
• Safety recommendations : Do not swallow; avoid extra-large quantity inhalation.
  
  
• CAS Reg. No. : 10 447-39-9 (HCl); 10 447-38-9 (base).
  
  
• Bibliography :
  
  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