cinanserin and tryptamine

The isolated perfused crop of Aplysia dactylomela was used to assess the effects of applied serotonin on 1st order small phasic contractions, 2nd order large tonic contractions, and 3rd order slow changes in tonus. Very low concentrations of serotonin may potentiate spontaneous contractions. Concentrations of the order of 10(-7) M serotonin may regularize "beating" of the crop by suppressing large tonic contractions while potentiating phasic contractions. Concentrations higher than 10(-5) M serotonin induce prolonged tonic contracture.

Topics: Action Potentials; Animals; Aplysia; Catecholamines; Cinanserin; In Vitro Techniques; Muscle Contraction; Muscle, Smooth; Periodicity; Serotonin; Tryptamines

In helically-cut strips of cerebral arteries isolated from dogs, serotonin, tryptamine, 5-hydroxytryptophan and tryptophan caused a dose-related contraction. The potency was in the order of serotonin greater than tryptamine much greater than 5-hydroxytryptophan = tryptophan. In femoral arterial strips, only serotonin and tryptamine produced contractions. In cerebral arteries, the dose-response curve for serotonin was shifted to the right and downward by treatment with cinanserin, whereas in femoral and mesenteric arteries, the curves were shifted to the right. The contractile response of cerebral arteries to tryptamine was attenuated by cinanserin in concentrations above 10(-7) M; however, 10(-5) M was required to significantly reduce the response of femoral arteries. Phentolamine reduced the contractile response of femoral arteries to tryptamine, but not the response of cerebral arteries. It may be concluded that the different antagonism of cinanserin against the serotonin action on cerebral and femoral arteries is due to the ability of high concentrations of serotonin to induce relaxations of cerebral but not femoral arteries or to the different nature of receptors. Tryptamine appears to elicit contractions of cerebral arteries via a stimulation of tryptamine receptors, but elicit those of femoral arteries via stimulation of both alpha-adrenergic and tryptamine receptors. Whether or not receptors for serotonin and tryptamine are the same was not determined.

Topics: 5-Hydroxytryptophan; Animals; Cerebral Arteries; Cinanserin; Dogs; Female; Femoral Artery; In Vitro Techniques; Male; Mesenteric Arteries; Methysergide; Phentolamine; Serotonin; Serotonin Antagonists; Tryptamines; Tryptophan; Vasoconstriction

Tryptamine was applied directly into the spinal subarachnoid space of rats via permanently indwelling cannulas. Changes in pain-perception were measured by changes in the latency of the tail-flick in response to a radiant heat source of low intensity. While an intrathecal injection of serotonin has been previously shown to be analgesic, exogenous tryptamine produced dual effects on the pain-threshold, depending on the dose of tryptamine injected. Low doses of tryptamine (100 and 200 micrograms/rat) injected intrathecally onto the sacral area of the spinal cord appeared to be hyperalgesic by significantly decreasing the average tail-flick latency by 5 min after injection. Administration of the serotonin antagonist methysergide alone was without effect on the average tail-flick reaction time when injected either intrathecally or subcutaneously. However, pretreatment with either methysergide or cinanserin not only failed to inhibit tryptamine's potentiation of nociception, but actually enhanced the hyperalgesia produced by tryptamine. In contrast, a dose of 400 micrograms of tryptamine significantly increased the average tail-flick latency, suggesting an analgesic effect at this higher dose. This analgesic effect of 400 micrograms of tryptamine was completely inhibited by subcutaneously administered methysergide, while intrathecally injected methysergide produced even greater decreases in the tail-flick latencies after this high dose of tryptamine. These results suggest that tryptamine, although it differs from serotonin by only one hydroxyl group, may play a role in nociception which is opposite that played by serotonin.

Topics: Animals; Cinanserin; Dose-Response Relationship, Drug; Drug Interactions; Hyperalgesia; Hyperesthesia; Injections, Spinal; Male; Methysergide; Rats; Rats, Inbred Strains; Serotonin; Tryptamines