trans

388 NEUROTRANSMITTERS
myoexcitation is associated with an acetylcholine-induced
inward current, indicating
the presence of a nicotinic-like acetylcholine
receptor on these muscles. As mentioned
previously, acetylcholine effects on other flatworm
musculature has been predominantly
inhibitory.
The actions of acetylcholine on flatworm
musculature are described most frequently as
inhibitory, but the nature of the receptors mediating
these responses is not clear. Cholinergic
receptors on the tegument of schistosomes
are also present, but the nature and function
of these receptors also remain unknown.
Cholinergic compounds have been used
therapeutically for the treatment of cestode
infestations in the dog and horse. The selective
muscarinic agonist, arecoline, is an old
and still effective treatment for Echinococcus
granulosus and Dicrocoelium dendriticum in
the dog, but pilocarpine, another muscarinic
agonist, is without effect on these cestodes.
Although the effects of arecoline have been
known for a long time, treatment is not without
side-effects on the host. The muscarinic
effects produce uncomfortable colic in the
host as a result of the stimulation of peristalsis.
The anti-nematodal drug, pyrantel, also has
effects against tapeworms in horses. The effects
of arecoline and pyrantel are further confirmation
of the presence of cholinergic receptors in
cestodes, and the anti-cestodal pharmacology
confirms the unique nature of the receptors;
atropine is not effective as an antagonist, and
pilocarpine is not effective as an agonist like
arecoline. The effect of cholinergic compounds
as therapeutic agents against parasitic trematodes
has not been demonstrated, and may be
limited by the distribution of the drug following
oral administration and the ability of the
parasite to survive in a paralyzed state until
the drug is cleared from the host. Parasites
in the gastrointestinal tract may find it more
difficult to survive such paralysis, because the
continuous peristalsis would tend to drive the
parasite out of the intestine. Such effects may
not be observed in the bile ducts if cholinergic
agonists were applied to F. hepatica. Below,
three cholinergics with anti-cestodal activity
are considered.
Pyrantel
Pyrantel, a cholinergic agonist more normally
used in animals for the treatment of gastrointestinal
nematode infections, is effective for
the treatment of some cestode infections in
the intestine. It is licensed for the treatment of
Anoplocephalia perfoliata in horses. Effects
against other cestodes and trematodes have
not been described.
Arecoline
Arecoline (Figure 15.20) is an old treatment for
cestode infections that is effective against
Echinococcus granulosus and Dipylidium caninum
in dogs. Arecoline stimulates the cholinergic
receptors on the muscle of the scolex and
body to produce paralysis. Arecoline also has a
purgative effect on the host animal, due to its
muscarinic action. The combination of purgation
and paralysis of the tapeworm is effective.
The purgation is severe in some animals, and
so newer therapeutic agents are preferred.
FIGURE 15.20
COOCH 3
N
CH 3
Chemical structure of arecoline.
BIOCHEMISTRY AND CELL BIOLOGY: HELMINTHS