a nicotinic cholinoreceptor antagonist at the neuromuscular junction; curare-like ganglioblocker.

Bis-quaternary quinuclidine derivative‚ C₃₄H₅₀Cl₂N₂.4H₂O ‚ synthetic.

Curare-form competitive anti-depolarizing muscle relaxant. Used for muscle relaxation and controlled breathing under narcosis during surgical operations. Can be used for tracheal intubation.

In urethane narcotized cats i.v. (single pulse 3 V‚ 0.1 msec‚ 0.2 Hz‚ stimulation of the peripheral end of sciatic nerve): 0.1mg/kg decreases the muscle contraction amplitude for 5-10 min with slight breathing suppression. 0.2-0.3mg/kg causes a complete neuromuscular block for 5-15 min; strong breathing suppression or apnoe starting from 0.2mg/kg. 0.3mg/kg stops the breathing with lethal end. Under artificial breathing no lethality at 75mg/kg and more.



Influence of Diquine on neuromuscular synapses lability: series (15 sec series‚ 30 sec pause) of 0.1msec impulses of different frequency (1-30-100-200 Hz): pessimal slow-down at 0.05mg/kg at 100Hz‚ 0.075-0.1mg/kg at 30Hz.



On vegetative ganglia 0.3-0.5 mg/kg stimulates the nictiating membrane on pre-ganglion cervical nerve stimulation. 1-2mg/kg slows down the neuronal transmission - two phase effect. 0.5-1mg/kg decreases the depressor reaction at vagal stimulation‚ no hypotension for ACh after Diquine administered at these doses. 3mg/kg completely blocks the parasympathetic ganglia for 10-15 min and causes 20-40mm Hg of arterial pressure drop for 10-30 min. In the absence of artificial breathing‚ 0.2-0.4 mg/kg stops breathing.



Causes gradual fading of cardiac activity; with artificial breathing even 75 mg/kg was not lethal despite 80-120mm Hg pressure drop. No pace rate or pulse change; arterial pressure normalization after 3-4h.



Competitive curareform drug Diplacin increases‚ while depolarizing drugs Ditilin and Decamethonium decrease Diquine potency. 2-5 mg/kg causes no significant arterial pressure change. 0.2 mg/kg does not change nictiating membrane contraction caused by 0.02-0.025 mg/kg of cytisine. 0.0001mg/kg does not diminish ACh effect on frog rectum [3].



In non-narcotized rabbits i.v.: 0.05-0.06 mg/kg causes "head drop" after 4-9 min; 0.08-0.1 mg/kg-complete muscle relaxation;0.15-0.2 mg/kg stops the breathing. With artificial ventilation spontaneous breathing recovery in 3-5 min and with muscle relaxation for 15-30 min (IC50 = 0.062 mg/kg).



In humans i.v.: 1mg/kg causes muscle relaxation for ~10 min with some breathing suppression. 1.2-1.5 mg/kg: 15-20 min myorelaxation‚ for some patients 4-5 min apnoe. 1.8-2 mg/kg: complete muscle relaxation and 17-20 min apnoe; at 2 mg/kg beginning of muscle relaxation in 1.5-2 min‚ complete muscle relaxation and apnoe in 2.5-4 min. Gradual decurarization: after restoration of spontaneous breathing‚ muscle relaxation continues for 15-20 min; in 25-30 min complete recovery of muscle tonus and breathing. To prolong the action of Diquine the repeated dose must be 1.5-2 times lower. The effect is antagonized by PROSERINE. No effects on blood pressure‚ moderate tachicardia [4].



For comparative information see the attached table.

1. Michlina E.E. et al., Khim-Farm. Zh. (1961) (Russian) 31:2609-2613
2. Machkovsky M.D., Sadritdinov F., Farm.Toksikol . (1962) (Russian). 25(6), 685-691
3. Sadritdinov F., Farm.Toksikol (1962) (Russian). (SAR for polymethylene bis-quinuclidiniums) 25(3):327-335
4. Mashkovsky M.D. Lekarstvennye Sredstva (Drugs) -Moscow, Meditzina, (1984). 1:261