Pancuronium bromide and other steroidal neuromuscular blocking agents containing acetylcholine fragments

Synthesis of 16E-[3-methoxy-4-(2-aminoethoxy)benzylidene]androstene derivatives as potent cytotoxic agents

“…The reaction mixture was further refluxed for 6 h with continuous stirring until the reaction was completed (monitored by TLC). The reaction mixture was cooled, filtered and solvent was removed under reduced pressure to obtain the corresponding oily residue (3)(4)(5), which was used as such for subsequent reaction.…”

“…Further, as expected the synergistic activity out of these hybrid steroidal structures was also obtained. Interference with neuromuscular transmission has been reported to be a side effect of potent antitumor agent vincristine [4]. Comparison of its molecular structure with potent neuromuscular blockers indicated drug-receptor similarities owing to presence of common structural features like well-spaced two tertiary amino groups in lipophilic * Corresponding author.…”

Neuromuscular Blocking Drugs: Discovery and Development

“…Figure 1 Acetylcholine (a) and suxamethonium (b) that the muscarinic receptor activity resided in the quaternary group at one end (the A ring) and the neuromuscular blocking activity resided separately in the other quaternary group (the D ring) 27 . By demethylation of the A ring nitrogen Savage came up with vecuronium, a 'clean drug' devoid of cardiac effects.…”

Recent Advances in Neuromuscular Blocking Agents

“…While the action of nondepolarizing NMBs can be reversed by ACh-esterase inhibitors such as neostigmine, the effect of suxamethonium is terminated by a rapid degradation of the dimeric ACh-like molecules by plasma cholinesterases resulting in a very short duration of action under 5 minutes. Based on the structure of another arrow poison alkaloid malouetine, scientists at Organon developed the non-depolarizing aminosteroidal muscle relaxant pancuronium bromide (6) (Pavulon ® , 1968) [11] with an approximately five-fold higher potency than (+)-tubocurarine 1 and a shorter serum half-life time (t 1/2 = 107 min) due to the metabolitic inactivation by hydrolysis of both lateral ACh-like moieties [12]. Other advantages of pancuronium over (+)-tubocurarine are lack of histaminereleasing and of ganglion-blocking activity.…”