Opiates, enkephalins and racing horses

Abstract

The narcotic analgesics or morphine-like drugs have long been known to be effective stimulants in horses, and they have an equally long tradition of use in racing horses. Since their use is almost invariably illegal, people who use these drugs play a cat and mouse game with the analytical chemist. In this game, drug users seek to identity narcotics which the chemist cannot detect, while the chemis~ tric.~ to develop analytical methods which can detect minute amounts of these narcotic drugs. Discovery of the endogenous opiates or enkephalins in the mid-1970s, however, introduced a number of intriguing new possibilities concerning the use of narcotic drugs in racing horses. The enkephyalins are small molecules, approximately the same size as morphine, which all mammals have in their central nervous systems. In mammals , the enkephalins produce physiological effects similar to those of morphine because morphine is a structural analog of the enkephalins. While discovery of production in horses and other mammals of agents which are, in essence an animals own morphine was surprising, it also raised some interesting possibilities about the illegal use of these agents in racing horses. The basic thought about the enkephalins is that it might be possible to administer them to horses and thereby produce all the stimulant and narcotic effects of the analgesic drugs. However, since the enkephalins are present in all horses, simple detection of an enkephalin or enkephalin metabolite would noh per se, be evidence of a medication offense because these agents are likely normal constituents of horse urine. In the discussions which have often surrounded the medication issue, the spectre of these supposedly super-effective, super-difficult-todetect drugs has occasionally been raised. While these scenarios may sound plausible to the uninitiated, there are a number of potential problems with them. In the first place, all neurohormones such as the enkephalins break down readily. They must do so, for if they did not, the brain would not be able to function normally. For this reason, giving the enkephalins by any route is likely at best to produce quite short-lived effects. Therefore, after injection, the enkephalins probably persist for only a few minutes. making them distinctly poor illegal medications. In recent experiments in our laboratory, we were unable to produce measurable pharmacological effects by injecting lcucine enkephalin either intravenously or directly into the brain of horses. Chemists can modify the enkephalins in such a way that they are not readily broken down. These agents, which are chemically distinguishable from the enkephalins, de have much longer pharmacological actions than the enkephalins. However, the same chemical modifications that make them longer acting allow the chemist to distinguish between these synthetic enkephalins and the enkephalins. These agents are, therefore, in principle at least, amenable to chemical identification as being to the natural horse. Finally, one might ask, what are the pharmacological actions of these modified enkephalins likely to be? Do they indeed mimic the actions of morphine in the horse and produce locomotor stimulation and analgesia? To test this hypothesis, we injected methionine-enkephalin into horses. Methionine enkephalin, a typical long-acting analog of enkephalin, had no significant effect on horses when given IV. The reason for this lack of effect appears to be that enkephalins penetrate the central nervous system poorly and are therefore ineffective by the IV route. It appears, therefore, that even the long-acting enkephalins are poor candidates for illegal use because they are ineffective by the IV route and, in principle at least, chemically identifiable as being foreign to tile horse. In a final at tempt to determine the effects of these longacting enkephal ins in horses, we administered