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Section IBasic principlesNon-depolarizing muscle relaxants
Bis-benzylisoquinoliniums
Bis-benzylisoquinoliniums is one of the two groups into which the non-depolarizing
muscle relaxants can be divided, the other being the aminosteroids (see below).
These are based on the structure of the naturally occurring drug tubocurarine. They
are so named from their underlying structure of two (hence the bis-) isoquinolinium
structures, linked through a carbon chain containing two ester linkages. The iso-
quinolinium structure is related to papaverine, which is a smooth muscle relaxant.
Features of the moleculecular structure of atracurium are the distance between qua-
ternary nitrogens (approximately 1 nm), the heterocyclic, bulky ring structures and
the reverse orientation of the ester linkages that favours Hofmann degradation. In
mivacurium the ester linkages are oriented the opposite way, which does not allow
Hofmann degradation to occur. The nitrogen atom in each isoquinolinium group is
quaternary, so the molecules are permanently charged and are presented as a salt.
Multiple isomers exist, with differing activity (see Chapter5).Aminosteroids
The steroid nucleus is a complex polycyclic hydrocarbon structure. It is important to
recognize that many hormones have this basic structure as well as many drugs. It has
been popular as a drug skeleton because it is relatively inflexible. The aminosteroid
non-depolarizing muscle relaxants are steroids, as is the intravenous agent althesin
and the corticosteroid hormones. It is worth recognizing the numbering of the car-
bon atoms, since this will help identify metabolites and substitutions especially
for muscle relaxants. Importantly, the steroid nucleus is not readily water-soluble;
this requires hydrophilic substitution. In the aminosteroid family, not all are read-
ily water-soluble and vecuronium has to be presented as a lyophilized preparation
to ensure its stability (rapid freezing and dehydration of the frozen product under
a high vacuum). Important features are the distance between nitrogen atoms, the
acetyl groups ester linked to the 3 and 17 positions and the bis-quaternary structure
of pancuronium but the monoquaternary structure of vecuronium and rocuronium
with the N- in the 2 position protonated at pH 7.4.