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Outschoorn AS, Jacob J.
“A study of antagonists of 5-hydroxytryptamine and catecholamines on the rat's blood pressure.”.
Brit.J.Pharmacol.. 1960;15:131.
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Abstract
In the rat (urethane-barbiturate anesthesia) serotonin (5-hydroxytryptamine = 5-HT) has a depressor, pressor or biphasic depressor/pressor effect the response depending on the control blood pressure level and on dosage. At medium blood pressure and dosage levels it is predominantly depressor. . LSD (10-40 mcg/100 Gm. i.v.) diminished the depressor effect of 5-HT more than the pressor effect. It also diminished the pressor effects of epinephrine (0.1-0.2 mcg.) and norepinephrine (0.05-0.1 mcg.) i.v. Antagonism against 5-HT was greater than that against the catecholamines, and that against epinephrine greater than against norepinephrine. Large doses of LSD (35-80 mcg/100 Gm.) abolished the depressor effects of 5-HT leaving only (reduced) pressor effects ("reversal"). These doses suppressed or greatly diminished the pressor effects of the catecholamines, especially that of epinephrine, while the depressor effect of isoprenaline (0.05-0.1 mcg. i.v.) was not affected. . Dihydergot (DHE) in small doses (5-10 mcg/100 Gm. i.v.) diminished the depressor effect of 5-HT and the pressor effects of the catecholamines. The anti-5-HT activity was only slightly increased by raising the dose of DHE to 25 mcg/100 Gm. and not further augmented by raising the dose up to 80 mcg/100 Gm. On the other hand, antagonism against the pressor effects of epinephrine and norepinephrine and the depressor action of isoprenaline increased with rising doses of DHE. . Thus with LSD the anti-5-HT effect was more marked than the antiadrenergic action while with DHE the anti-5-HT and antiadrenergic activities were about equal. . LSD and DHE reduced the depressor effect of adenosine, LSD, but not DHE, sometimes unmasking a pressor effect. The depressor action of ACh (0.25-0.5 mcg. i.v.) was not affected by LSD and DHE but reduced or abolished by atropine (0.1 mg/100 Gm. i.v.). After a total of 0.2 mg/100 Gm. of atropine the depressor effects of 5-HT were somewhat reduced and the pressor effect (once) slightly potentiated. . Regarding other antagonists: Dibenamine, 1-benzyl-5-methoxy-2-methyltryptamine and a dichloro analogue of isoprenaline antagonized both 5-HT and catecholamines, the tryptamine derivative being more active against 5-HT and dibenamine and the isoprenaline derivative more active against the catecholamines. . The antagonists fell into 2 groups according to their action against the 2 effects (pressor and depressor) of 5-HT: LSD and the dichloroisoprenaline acted preferentially against depressor effects, the tryptamine derivative and dibenamine preferentially against pressor effects. DHE was not assignable to either group. It had a pressor effect of its own which made it difficult to determine its action against pressor effects of 5-HT.
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