a semirigid molecular probe for different ion channels or receptors. Na⁺ channels blocker. Represents a new class of anti-histaminic (nonH1 or H2) and anti 5-HT anti-allergic drugs: potential antagonist of H-3 histamine and serotonine (non 5-HT2) receptors. Anti-pruritic. Diamine oxidase activator.

Quinuclidine derivative, C₂₂H₂₇NO.HCl.2H₂O, synthetic.

• Molecular Weight : 393.96 Da.
  
  
• Melting Point : 277-279 °C (decomp.).
  
  
• Solubility in : sparingly in water (25°C, 4 mM); better in 50% ethanol.
  
  
• Purity min. : min. 98 %.
  (TLC [on "Silufol UV-254", MeOH-NH3 (25 %) 10:1, Rf = 0.14. Visualization by UV-light followed by Dragendorff's reagent.], NMR[CD3OD]).
  
  
• Physical Form : colorless crystal powder.
  
  
• Chemical Name : (3-Quinuclidinyl)di(2-MethylPhenyl)Carbinol hydrochloride dihydrate, (3-quinuclidinyl)di(o-tolyl)methanol hydrochloride dihydrate.
  
  
• Biological Activity : For detailed information see the attached tables and abstracts.
  
  Ion channels agent.
  On Na⁺ channels (CA1-CA3 region of rat hippocampus neurons), 2.5x10^-4 M results in 100 % blocking effect, 2x10^-6 M in 50%.
  On isolated throat ganglia neurons of the snail Limnea stagnalis (patch-clamp whole-cell recording):
  * On K⁺ channels: meagre reversible blockade at 10^-5 M.
  * No effect on Ca²⁺ or Cl^- channels.
  
  Anti-allergic.
  Non-sedative low anti-cholinergic anti-histaminic of prolonged action combined with anti-serotonine activity: aerosol histamine bronchoconstriction prevention in guinea-pig : 80-90 % at 2 mg/kg, the same for 5-HT : > 2 mg/kg. (Phencarol: 0.2 and 1 mg/kg respectively). Prolonged action (3-4 hours) and enhanced anti-5-HT activity compared to Phencarol (1.5 hours); efficient against itches [1-3]. Non H-1, H-2 or 5-HT2 blocker: no binding to rat cortex H-1, H-2 receptors, 5-HT-2 receptors [4].
  
  Low affinity to M-AChR.
  pIC₅₀ [3H]-quinuclidinyl-3-benzylate, rat brain (M-1)/heart (M-2) 5.63/5.33; guinea pig ileum 4.9 (Methylfurmethide), 5.5 (ACh); Pridinol 7.3/6.8, Atropine 9.0/10.0.
  Good penetration of biological membranes.
  Diamine oxidase activator (75 mg/kg p.o., rat lung, 60 min +52%, 180 min +44%) [5-6].
  weak anti-AChE activity in vitro (human erythrocytes) Ki. 10⁴ = 2.60, type of inhibition: mixed competitive/non competitive.
  
  
• Toxicity (LD₅₀) : mice (orally): 650 mg/kg.
  mice (i.v.): 68 mg/kg.
  
  
• Storage recommendations : Stable in dry state and solution (up to 150 °C). Dissolves slowly, use heating or boiling. Solution for use: 10-3 M (2 mg in 5.01 ml).
  
  
• Safety recommendations : Do not swallow, avoid extra-large quantity inhalation.
  
  
• CAS Reg. No. : 57 734-70-0 (HCl); 57 734-69-7 (base)
  
  
• Bibliography :
  
  1. Kaminka M.E. et al., Khim. Farm. Zh. (1976). 10(9):22-27
  2. Kaminka M.E. et al., Drugs of Today (1988). 24(10):701-703
  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. Baumanis E.A. et al., Farm. Toksikol (1980) (Russian). (1):36-41
  6. Mashkovsky M.D. et al., "Further developments in research on the chemistry and pharmacology of synthetic quinuclidine derivatives." Progr. Drug. Res., (1983). 27:9-61