Using tricaine, we tested the response of DBL-1 variants to this larger Cinepazide maleate anesthetic over time. We found that tricaine affects DBL-1 overand under-expressing animals in manner similar to levamisole, where dbl-1 animals are resistant, while dbl-1 animals are more sensitive to tricaine-induced paralysis. IP2P, a smaller anesthetic with a molecular weight of 152, acts as an anesthetic by eliminating neural activity and blocking muscular contraction. We asked if DBL-1 variant animals would display altered sensitivity to this lower molecular weight anesthetic. We found that dbl-1 mutant animals are more sensitive to IP2P than wild-type animals. Notably, we discovered that long dbl-1 animals are as sensitive as wild-type animals to the paralyzing effects of IP2P. Unlike the other anesthetics tested here, the nematode anesthetic sodium azide acts by inhibiting the electron transport chain. Further differentiating these anesthetics, sodium azide is much smaller, having a molecular weight of 65. We asked if DBL-1 variant animals display an altered response to this low molecular weight anesthetic. While sodium azide is commonly used for imaging at doses of 10�C 25 mM, which anesthetizes nematodes quickly, we chose a lower dose, 1 mM, to test for differences in sodium azide sensitivity in dbl-1 under- and Mechlorethamine hydrochloride over-expressing strains in our 90-minute assay. Similar to their behavior on the other tested anesthetics, small dbl1 animals display a more sensitive response to sodium azide. Like the result with IP2P, we discovered that long dbl1 and lon-2 animals are at least as sensitive to the paralyzing effects of sodium azide as wild-type animals. These results show that loss of DBL-1 results in hypersensitivity to multiple drugs of varied size and mode of action, while animals with enhanced DBL-1 signaling are resistant to the higher molecular weight drugs tested in this study, levamisole and tricaine. This data suggests that a lower dose of DBL-1 decreases barrier function, allowing higher molecular weight molecules to access targets, and lower molecular weight molecules increased access to targets.