Some natural alkaloids, e.g. capsaicin and camphor, are known to induce a desensitization state, causing insensitivity to pain or noxious temperatures in mammals by acting on TRP receptors. Our research, for the first time, demonstrated that a phenomenon of pharmacological blockade of heat sensitivity may operate in American cockroach, Periplaneta americana (L.). We studied the escape reaction time from 50°C for American cockroaches exposed to multiple doses of different drugs affecting thermo-TRP. Capsaicin, capsazepine, and camphor induced significant changes in time spent at noxious ambient temperatures. Moreover, we showed that behavioral thermoregulation in normal temperature ranges (10-40°C) is altered in treated cockroaches, which displayed a preference for warmer regions compared to non-treated insects. We also measured the levels of malondialdehyde (MDA) and catalase activity to exclude the secondary effects of the drugs on these processes. Our results demonstrated that increase in time spent at 50°C (five versus one trial at a heat plate) induced oxidative stress, but only in control and vehicle-treated groups. In capsaicin, capsazepine, menthol, camphor and AITC-treated cockroaches the number of exposures to heat had no effect on the levels of MDA. Additionally, none of the tested compounds affected catalase activity. Our results demonstrate suppression of the heat sensitivity by repeated capsazepine, camphor and capsaicin administration in the American cockroach.