Page 1143 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

Ionophores Chapter | 78 1075

VetBooks.ir been no reports of investigational use of ionophores in coordination and depressed acetic acid writhing occurred at
30 mg/kg. In cats, immobilized by D-tubocurarine or anaes-
humans.
thetized with urethane and α-chloralose, an oral dose of
30 mg/kg produced no effect on the electroencephalogram
PHARMACOLOGY/PHARMACOKINETICS and the spinal reflex. At the same dose in anaesthetized

Pharmacology cats, the heart rate, electrocardiogram, respiration and blood
pressure responses to epinephrine, acetylcholine (ACh), his-
Investigational studies were conducted to determine if tamine and contractions of the nictitating membrane in
ionophores had any undesirable pharmacological proper- response to electrical stimulation of the cervical sympa-
ties. A series of general pharmacology studies was con- thetic ganglion were not affected. Charcoal meal transit in
ducted with monensin (Novilla, 2004). The studies with mice was not affected by an oral dose of 10 mg/kg while
monensin assessed its effects on the central, peripheral 30 mg/kg significantly depressed the transit rate. Gastric
and autonomic nervous systems and the digestive, respira- secretion was not affected by an oral dose of 30 mg/kg in
tory and cardiovascular systems. The test systems with rats. In isolated guinea pig illegal preparations, monensin in
doses and route of administration and no-observed-effect- a bath concentration of 10 25 g/mL had no antagonistic
level (NOEL) are shown in Table 78.1. effects on contractures induced by ACh, histamine and bar-
In mice, an oral dose of 10 mg monensin/kg produced ium chloride. In the rat anticarrageenan edema test, monen-
no significant effects on general behaviors, coordinating sin given orally at 30 mg/kg did not significantly inhibit
activity in skeletal muscles, electroshock seizures and acetic carrageenan-induced edema of the hind paw.
acid writhing. However, slight sedation, decreased sensitiv- The studies targeting specific organ systems of labora-
ity to tactile stimulation, slight depression of muscular tory animals indicated that monensin at a dose of 10 mg/kg

TABLE 78.1 General Pharmacology Studies on Monensin

Test System Species Monensin Dose (mg/kg) Route NOEL (mg/
kg)
General behavior Mouse 0, 10 and 30 Oral 10
Coordinating activity of Mouse 0, 10 and 30 Oral 10
skeletal muscles
Antielectroshock seizures Mouse 0 and 30 Oral 30
Analgesic effect Mouse 0, 10 and 30 Oral 10
Spinal reflex Cat 0 and 30 Oral 30
Electroencephalogram Cat 0 and 30 Oral 30
(D-tubocurarine immobilized)
Circulatory, respiratory and Cat 0 and 30 Oral 30
autonomic effects
Charcoal meal transit Mouse 0, 10 and 30 Oral 10
Gastric secretion Rat 0 and 30 Oral 30
Isolated ileum Guinea pig 1 3 10 25 g/mL In vitro 1 3 10 25 g/mL
Carrageenan-induced edema Rat 0 and 30 Oral 30
Cardiovascular study Dog 0, 0.0069, 0.0138, 0.0345, 0.0690 and 0.138 Intravenous 0.0345
(conscious)
0, 0.138, 0.345, 0.690 and 1.38 Oral 0.345 a
Cardiovascular and Dog 0, 0.00069, 0.0014, 0.0035, 0.0069, 0.014, Intravenous 0.0035
respiratory effects (anesthetized) 0.035, 0.069, 0.14, 0.35, 0.69 and 1.4
Cardiovascular and Pig 0, 0.00069, 0.0014, 0.0035, 0.0069, 0.014, Intravenous 0.0035
respiratory effects (anesthetized) 0.035, 0.069, 0.14, 0.35 and 0.69
a
Based on transient increases in coronary blood flow at doses $ 0.69 mg/kg.