Interactions of 5-hydroxytryptamine and tricyclic antidepressants in the rat stomach strip and the guinea-pig ileum.
The interactions of the tricyclic antidepressants, amitriptyline and desipramine with 5-hydroxytryptamine (5-HT) were studied in the guinea-pig ileum and in the rat stomach strip. The tricyclics blocked the contractile response of the guinea-pig ileum and severely depressed the maximum [amitriptyline greater than desipramine (DMI)], however, they potentiated (DMI greater than amitriptyline) 5-HT-induced contractions of the RSS. The potentiation induced with DMI seems to be a combination of uptake inhibition and some post-receptor sensitization whilst amitriptyline-induced potentiation may be due to the former. Higher concentrations of the tricyclics contract the RSS. These contractions were absent in reserpinized RSS. Reserpinization reduced the potentiation after tricyclics and DMI was unable to enhance maximal concentrations of 5-HT, i.e. the post-receptor effect of DMI seems to have been abolished. It is concluded that whilst the tricyclics may be irreversible antagonists of 5-HT in the guinea-pig ileum, they potentiate the effect of 5-HT in the RSS by uptake inhibition, and, in the case of DMI, some additional post-receptor effect.
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D051381:Rats; D012110:Reserpine / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology*; D013270:Stomach / Q000187:drug effects
D000929:Antidepressive Agents, Tricyclic; D012701:Serotonin; D012110:Reserpine