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VetBooks.ir Chapter 78

Ionophores

Meliton N. Novilla

INTRODUCTION field researchers whose work has been omitted or inadver-
tently missed.
Ionophores are compounds that form lipid soluble,
dynamically reversible complexes with cations and by
this means facilitate specific ionic transport across bio- BACKGROUND
logic membranes (Pressman, 1976; Reed, 1982; Taylor
et al., 1982). There are two major subclasses of iono- Presently, seven carboxylic ionophores are approved for
phores, (1) neutral ionophores, which are highly toxic the control of coccidiosis and promotion of growth and
because they form charged complexes that are capable of feed efficiency in several animals of economic impor-
perturbing biologic membranes and action potentials, and tance. Since their introduction carboxylic ionophores have
(2) carboxylic ionophores, which form zwitterionic com- played significant roles in livestock and poultry produc-
plexes with cations and promote electrically neutral cation tion systems throughout the world. Monensin, first intro-
exchange diffusion that is tolerated better in intact organ- duced as Coban in the United States for the control of
isms. The ionophoric activity may alter normal concentra- coccidiosis in chickens in 1971, was later marketed in
tion gradients resulting in cellular ion imbalance, pH 1975 as Rumensin to promote growth and/or increase
change, calcium overload, lipid peroxidation, and disrup- feed efficiency in cattle. Similarly, lasalocid has been
tion of plasma membranes. The alteration in the mem- marketed since 1977 as Avatec for chickens and since
brane transport of ions is the basis for the metabolic, 1982 as Bovatec for cattle. Later, laidlomycin (Cattlyst)
organic, and functional effects of this class of compounds. was used in cattle and salinomycin (Bio-cox, Sacox),
Since their pharmacologic activity is dose related, the use- narasin (Monteban, Maxiban), maduramicin (Cygro), and
fulness of carboxylic ionophores is based on selective semduramycin (Aviax) were used in chickens respectively
toxicity to protozoan parasites and bacteria and margins (Fig. 78.1).
of safety in the approved target species. Desirable Other benefits of ionophore use include (1) reduction
effects occur when animals are provided feed containing of coccidial oocyst discharge in ruminants, (2) prevention
approved dosage ranges, but higher levels may result in of acute bovine pulmonary edema and emphysema, (3)
adverse effects. decreased incidence of bloat, (4) prevention of ruminal
This chapter attempts to provide an overview of iono- lactic acidosis, and (5) amelioration of ketosis in lactating
phores as they relate to veterinary medicine, with empha- dairy cows (Duffield et al., 2002; Heuer et al., 2001;
sis on ionophore-induced toxicity. Large numbers of Parker et al., 1986; Nocerini et al., 1985). The reduction
ionophore safety and toxicity studies have been conducted of deaths in some cattle herds has been hypothetically
in support of marketing approval, but results of many related to the reduction of indigestion, metabolic stress,
studies are unpublished. For this reason, information pre- bloat and enterotoxemia associated with monensin
sented was gleaned from published laboratory and field feeding.
reports of toxicoses in various species of animals, avail- Potential uses of the ionophores are under experimen-
able reviews and Freedom of Information summaries tal investigation in many parts of the world and off-label
obtained from the US FDA. However, due to space uses of some ionophores are known to occur. Monensin
limitations, not all information can be included, hence has been used for the control of toxoplasmosis in preg-
apologies are extended to laboratory scientists and nant sheep (Buxton et al., 1988), disseminated visceral

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