Figure 1. A cartoon showing the three major components of shivering: threshold (triggering core temperature), gain (incremental intensity increase with further core temperature deviation), and maximum intensity. The normal case is illustrated with a solid line. Antishivering drugs, such as meperidine or clonidine, may reduce muscular activity by decreasing any or all aspects of the shivering response. In this illustration, we consider the case of a drug that decreases the threshold, gain, and maximum shivering intensity (dashed line). The effect of drug administration on shivering intensity depends on the volunteer's core temperature. Shivering will be obliterated when the drug reduces the threshold to less than body temperature (A). Shivering intensity, however, will be substantially reduced when body temperature remains less than the new shivering threshold but low gain restricts the amount of muscular activity (B). Finally, shivering will also be reduced even at very low body temperatures because maximum intensity is restricted (C). In a routine clinical trial, it would be difficult to determine which mechanism(s) contributed to a drug's anti-shivering action.