Strickland et al. (1992, 1994) studied the effects of ergot and loline alkaloids of E+ tall fescue on prolactin release by isolated and perfused (circulation of media through the cells) rat pituitary cells. The ergot alkaloids lowered prolactin concentrations and mimicked dopamine action. The use of a D2 dopamine receptor antagonist (domperidone) blocked the effect of the ergot alkaloids and prevented their prolactin-lowering effect. Domperidone is a D2 dopamine receptor blocker that does not cross the blood-brain barrier. It does not elicit neuroleptic (central nervous system) side effects. Domperidone was administered orally (1.1 mg/kg body weight) to gravid mares grazing E+ tall fescue (Redmond et al., 1994). It resulted in an increase in serum prolactin and progestagens (progesterone and its derivatives) and provided what seemed to be nearly complete recovery of gravid mares from tall fescue toxicosis, with no observed neuroleptic side effects. Treated mares produced milk, had live and healthy foals, and their gestation length was similar to the calculated gestation length. Subsequently, a dose titration study (Fig. 17-2, 17-3, and 17-4) was conducted to determine the minimum effective dose of domperidone for treating tall fescue toxicosis (Redmond et al., 1994). Domperidone provided recovery from tall fescue toxicosis in gravid mares, and the minimum effective oral dose was 1.1 mg/kg body weight when administered daily for 30 d before foaling.

In a field study (Cross et al., 1999), domperidone was administered to 1423 periparturient mares grazing tall fescue in several U.S. states. Veterinarians, horse owners and managers reported the drug to be 95% effective in prevention of the signs of fescue toxicosis. Mares consuming the drug in a preventative mode did not experience increased gestation, dystocia, agalactia or lower than normal milk production, retained placentas, premature placental separations, or dead, weak, or dysmature foals, as had been observed in non-treated control mares.

 

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Fig. 17-2. Effects of varying levels of domperidone (1.1, 1.65, or 2.2 mg/kg, PO, SID) on mammary gland development in periparturient (near to parturition date) mares grazing E+ tall fescue pastures. Day -31 represents the average number of days before the calculated date of parturition when pretreatment samples were obtained (pretreatment samples obtained 1.2 d before initiation of drug treatment). Stars indicate first detectable difference (P < 0.05) from pretreatment values within treatment. Numbers indicate number of animals remaining in treatment group when sample was obtained (from Redmond, 1994).

Fig. 17-3. Effect of E+ fescue and domperidone (1.1, 1.65, or 2.2 mg/kg, PO, SID) treatment on serum prolactin levels in gravid mares. First detectable differences (P < 0.05) from pretreatment levels are indicated by stars. Unless otherwise indicated, data points represent four mares per treatment. Mares that were not showing signs of impending parturition 7 d after the calculated date of parturition, as determined by veterinary examination, were relocated to an E- pasture (from Redmond, 1994).

Fig. 17-4. Effect of E+ fescue and domperidone (1.1, 1.65, or 2.2 mg/kg, PO, SID) treatment on serum progestagen levels in gravid mares. First detectable differences (P < 0.05) from pretreatment levels are indicated by stars. Unless otherwise indicated, data points represent four mares per treatment (dagger indicates number of mares in the endophyte free group). Mares not showing signs of impending parturition 7 d after the calculated date of parturition, as determined by veterinary examination, were relocated to E- pasture (from Redmond, 1994).

 

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