Ganglionic-blocking activity

Hirsutine. Hirsutine (58) shows ganglion-blocking activity in cat superior cervical ganglion preparation (331), and it has a long-lasting depressive effect (332). Hirsutine also inhibits the ganglionic transmission of the dog urinary bladder (353, 334). 

In summary, 2-PAM I was found by Kunkel et al.11 to act as a depolarizing compound at the neuromyal junction and to have acetyl-cholinomimetic properties in large doses. It had some ganglionic blocking activity, but no direct effect on the CNS was detected. 

Brown, D.M. and Turner, D.H. (1959) Ganglionic blocking activity of tertiary sulfonium quaternary ammonium salts./. Pharm. Pharmacol., 11 (Suppl), 95T-102T. 

Metocurine has significantly less ganglion-blocking activity than D-tubocurarine (5) and much less of a tendency to provoke histamine release (6,7). It does not block cardiac muscarinic receptors at neuromuscular blocking doses... 

It is, however, pertinent to mention here that the internitrogen distance essentially constitute an important factor in many series of bisquatemary salts that possess ganglionic blocking activity. It is worthwhile to note that this distanee is dmost similar to that present in hexamethonium in its most extended configuration. 

Quaternary alkaloidal compounds associated with ganglionic-blocking activity have been identified in Magnolia extracts [63]. The alkaloids magnocurarine (41), magnoflorine (42), salicifoline (43), and d-tubocurarine (44) have demonstrated this effect in frogs. 

It can be seen from Tables 6 and 7 that conversion of some tertiary amines to the corresponding quaternary compounds induced or increased ganglion-blocking activity. 

Table 8 Ganglion-blocking activity and toxicity of some quaternary derivatives of dialkyl-aminoalkyl esters of 1,6-dimethylpipecolinic acid [187]...

Further investigations have shown that ganglion-blocking activity is retained on passing from the quinuclidine bicyclic system to the monocyclic system of piperidine (Table 8) [91, 187]. 

Table 11 Relationship of sympathetic and parasympathetic ganglion-blocking activity in some symmetrical hisquaternary quinuclidine compounds...

The quinuclidine derivative of this group (LXXXI a) showed httle activity in experiments on cats. As compared to (-h) tubocurarine and qualidile (LXXIXy) it was noticeably weaker in the head drop test in rabbits. Non-symmetrical diquaternary salts of the quinuclidine series having structure (LXXXII) (Table 14) showed weak curare-like and ganglion-blocking activity. 

Ganglionic blocking activity mg/kg, i.v. Doses reducing Doses by 50% the suppress-response of the ing hypo-cats nictitating tensive membrane to response electrical stim- to vagus ulation of the stimu-n. cerv. sup. lation... 

As the compound 47(5-N,N-dimethylamino-l,2,3 trithiane) was found to have the same strong insecticidal effect as Nereistoxin especially against rice stem borers, the ganglionic blocking activity by the compound 47 in adult male American Cockroach was investigated to reveal the insecticidal action of the compound. 

The compound did not show any ganglionic blocking activity or marked interference with the transmission of impulses in the cervical sympathetic chain. A significant depletion of catecholamines occurred from rat heart and brain, and the compound was also shown to interfere with the uptake of noradrenaline by the rat heart. In addition, it produced marked peripheral vasodilation, possibly by acting on adrenergic -receptors or by sensitizing these receptors to the action of adrenaline. 

Ganglion-blocking activity in the polymethylene iwtrimethyl-ammonium series is maximal when the two cationic heads are separated by five or six methylene-groups (Baton and Zaimis, 1949). Hexamethonium (7.24, n = 6), the most efficient ganglion-blocker in this series, competes with acetylcholine without causing any depolarization of the receptor (Baton and Berry, 1953). 

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