The rat isolated jejunum was used as a functional model to screen some antidepressant drugs at the "atypical" 5-HT(7) receptor. Mianserin acted as a surmountable antagonist of 5-CT with a PA(2) value of 8.22 +/- 0.33. The apparent PK(B) of maprotiline against 5-CT was 7.67 +/- 0.24 at 100 nmol/l, but higher concentrations suppressed the maxima. An apparent PK(B) could not be obtained for amitriptyline, because 10 nmol/l reduced the E(max) of 5-CT without causing parallel displacement. Higher concentrations of 30 and 100 nmol/l caused further suppressions. Amoxapine, loxapine and desipramine (each at 100 nmol/l) caused similar effects, suppressing the E(max) values to 5-HT by approximately 50%, while lower concentrations failed to cause parallel displacements. These results further extend the activity profiles of the drugs investigated.