Promethazine both facilitates and inhibits nociception in rats: Effect of the testing procedure

Abstract

The present study demonstrates that low doses of promethazine (1.25-5 mg/kg SC) dose-dependently facilitate nociception in the vocalization test in rats. However, this effect disappeared gradually with increasing dose, and in contrast, high doses (20-40 mg/kg SC) induced an antinociceptive effect. This indicates that promethazine, depending upon the biophase concentration, has the potential to interact with separate antagonizing or opposing functional systems, producing contrasting effects on nociception. The sigmoid Emax model was fitted to the observed composite effect, and dose-response characteristics for two opposite effects were described. In addition, when suprathreshold stimulation was used to evoke nociception, the stimulus amplified the hyperalgesic efficacy of promethazine but left the potency of this effect unaltered. In this experimental situation only negligible antinociception was observed. Our data thus show that for promethazine, the net effect on nociception in rats is not absolute but is balanced both by the biophase concentration and by the effectiveness of the stimulation used to evoke nociception.

Pain and U-Shaped Dose Responses: Occurrence, Mechanisms, and Clinical Implications

“…The findings of Paalzow and Paalzow (1982, 1983a, 1983b, 1985 are significant in several respects. Most importantly, they emphasized very robust study designs with respect to dose number and repeated measurements.…”

“…A biphasic dose response was also observed, consistent with the findings at the lower intensity. Based on the biphasic dose-response observations, Paalzow and Paalzow (1985) believed that apparent response contradictions in the literature with promethazine might be resolved, with most arising because of inadequate testing protocols (i.e., too few doses and time periods evaluated) to properly characterize the dose-time-response relationship.…”

“…As a result of these findings with yohimbine and apomorphine, Paalzow and Paalzow (1985) decided to assess the effects of promethazine, a phenothiazine derivative, on male SpragueDawley rats, using the same nociceptive test and electric stress level as employed in the apomorphine and yohimbine experiments. However, instead of using 11 doses and 10 time measurement points as in the earlier studies, 7 doses and 8 time points were employed.…”

The role of hormesis in the functional performance and protection of neural systems

“… Examples of neuroprotective effects displaying hormetic dose responses [ 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 ] …”