Effects of enkephalins versus opiates on locomotor activity of the horse

The enkephalins are small, pentapeptide neurotransmitter molecules which have reportedly been used in racing horses. In our experiments, D-Ala² Metenkephalinamide and leucine enkephalin were administered to horses intravenously (IV) and intracisternally (IC). Leucine enkephalin had little effect on locomotor activity by either route at doses of 0.01 mg/kg or less. Methionine enkephalinamide, an enzyme resistant enkephalin analog, had no significant effect when given IV (0.002 and 0.008 mg/kg). Other experiments involving intracisternal dosing with this long acting form at higher levels (0.005-.011 mg/kg), elicited an initial increase in locomotor activity, a rise in temperature, a marked increase in blood pressure, hyperventilation, the appearance of a rapid eye blinking reflex, lack of coordination and quivering. In contrast, dosing with fentanyl either IV (0.01 mg/kg) or IC (0.0002 mg/kg) produced a tenfold increase in locomotor activity without accompanying adverse clinical symptoms. The data suggest that very large doses of IV administered enkephalins or their analogs may be necessary to increase locomotor activity but such doses may also elicit a number of less desirable side effects.