Prostaglandin E<sub>1</sub> causes sedation and increases 5‐hydroxytryptamine turnover in rat brain

Haubrich, Dean R.; Pérez-Cruet, Jorge; Reid, Watson D.

doi:10.1111/j.1476-5381.1973.tb08224.x

Cited by 65 publications

(11 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, Bhattacharya & Sanyal(1978) reported that the threshold for leptazol seizure was reduced by prostaglandin El, Correspondence. which increases the 5-HT turnover and elevates the steady state concentrations of its neutral metabolites in the brain (Haubrich et al 1973;Fukumori et al 1980b).…”

Section: Discussionmentioning

confidence: 99%

Modulation of seizure pattern in the rat by neutral metabolites of indoleamines

Minegishi

Fukumori

Satoh

et al. 1981

Journal of Pharmacy and Pharmacology

View full text Add to dashboard Cite

The neutral metabolites of indoleamines (biogenic seizure latency time in normal animals after leptazol alcohols such as tryptophol and 5-hydroxytryptophol, administration. Tryptophol neither prolonged nor and biogenic aldehydes such as indoleacetaldehyde and shortened the latency to clonic seizure, but it signifi-5-hydroxyindoleacetaldehyde) have been reported to be cantly prolonged the latency to tonic seizure and the biologically active, i.e., to have sedative (Minegishi et al seizure latency time (35 and 94 %increases, respectively). 1979). sleep-inducing (Sabelli et al 1969; Taborsky Fig. 2 shows the effects of tryptophol in reserpinized 1971) and anticonvulsant properties (Fukumori et al animals. Treatment with reserpine potentiates the 1980a). Our recent finding that tryptophol and/or its convulsant properties of leptazol and shortens the metabolite indoleacetaldehyde decreased seizure seizure latency time (Chen et a1 1954). Thus, the dose of susceptibility in mice suggested the involvement of leptazol was reduced to 70 mg kg-' for better evaluation neutral metabolites of indoleamines in the regulation of of the tryptophol effect. The latency to the onset of seizure threshold (Satoh et al 1979a). On the other hand, it is well-established that the threshold for convulsion is modulated by a central aminergic system (Kilian & Frey 1973). In the present work, we examined the effect of centrally administered tryptophol on the components of leptazol (pentetrazo1)-induced seizures in normal and reserpinized rats, in the belief that neutral metabolites of indoleamines may be involved in the modulation of the seizure pattern by the 5-HT-ergic system. Materials and methodsMale Wistar rats, 180-220 g, were fitted with indwelling cannulae at least 1 week before the experiments, as described by Satoh et al (1979b). Tryptophol (1 pmol) was dissolved in 8 pl of 0.9 % w/v NaCl (saline) solution containing 25 % ethanol and injected intracerebroventricularly (i.c.v.) Control animals received equivolume injections of the vehicle alone. The vehicle had no effect on leptazol-induced seizure. Leptazol was dissolved in saline solution and injected intraperitoneally into normal animals at a dose of 100 mg kg-' and into reserpinized animals at 70 mg kg-', 1 min after the i.c.v. injection of tryptophol or the vehicle. Reserpine (2 mg kg-', i.p.) was dissolved in 0.3 M sucrose with a few drops of glacial acetic acid. After the leptazol challenge, latencies were recorded to the onset of (1) clonic seizure with loss of righting reflex; and (2) tonic seizure with hindlimb extension. The seizure latency time was estimated as the time interval between the first sign of clonic seizure and the tonic seizure, according to Weiss et al (1960). Fig. 1 shows the effects of tryptophol on the latencies to the onset of the clonic and tonic seizures, and the clonic seizure was also unaffected by i.c.v. injection of tryptophol in reserpinized rats. However, both the latency to tonic seizure and the seizure latency time were dramatically prolonged by...

show abstract

Section: Discussionmentioning

confidence: 99%

Modulation of seizure pattern in the rat by neutral metabolites of indoleamines

Minegishi

Fukumori

Satoh

et al. 1981

Journal of Pharmacy and Pharmacology

View full text Add to dashboard Cite

show abstract

“…In addition, Bhattachrya and Sanyal (24) demonstrated that the incidence of seizures after PTZ adminis tration was significantly reduced by pro staglandin E, which enhances 5-HT turnover (25,26). Kilian and Frey (9) suggested that although 5-HT played a role mediating both clonic and tonic components of PTZ seizures, it might be more crucially involved in the latter.…”

Section: Discussionmentioning

confidence: 99%

Suppression of pentylenetetrazol-induced seizures by hydralazine associated with 5-hydroxytryptaminergic system in rat brain.

1987

View full text Add to dashboard Cite

Abstract-The effects of hydralazine on the central nervous system were studied in rats. Administration of hydralazine (10 mg/kg, i.p.) transiently, but significantly suppressed the seizures elicited by pentylenetetrazol (PTZ). The suppressive actions were potentiated in the animals pretreated with either reserpine or p chlorophenylalanine, but not a-methyltyrosine.Methysergide, an antagonist of 5-hydroxytryptamine (5-HT) receptors, could abolish the effect of hydralazine on the tonic component of the seizures, but unlikely that on the clonic one. Although 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) levels in the brain were both sig nificantly increased after the administration of hydralazine, the increased levels of 5-HIAA reached the peak level earlier than those of 5-HT did. In 5-HT turnover, hydralazine did not change the 5-HT synthesis rate, but the drug inhibited the elimination of 5-HIAA from the brain. The accumulation of 5-HIAA after the inhibition of the acid transport system by probenecid was transiently, but sig nificantly increased in the animals treated with hydralazine.The potency of the suppressive effects of hydralazine on PTZ-induced seizures was in parallel with the rate of 5-HIAA formation in the brain. These results suggest that hydralazine might antagonize the PTZ-induced seizures at least partly by modulating the activation in the central 5-HT-ergic system.

show abstract

“…2), a highly selective EP 4 receptor agonist, and PF-04475270 (5), a novel ocular hypotensive compound. In order to develop medicinally relevant analogues, we embarked on the enantioselective synthesis of 8-aza-PGE 1 (7) and the 11-hydroxylated analogues (8 and 9) of the leads CP-734432 (4) and PF-04475270 (5) in light of the structure, medical usage [10] and side effects [11] of PGE 1 (alprostadil, 6).…”

Section: Introductionmentioning

confidence: 99%

Efficient asymmetric syntheses of alkaloids and medicinally relevant molecules based on heterocyclic chiral building blocks

Wang

Huang

2014

Pure and Applied Chemistry

View full text Add to dashboard Cite

In this report, we present recent progress in synthetic methodologies based on three heterocyclic chiral building blocks developed from our laboratories. The potential of these chiral building block-based methods in the concise asymmetric synthesis of alkaloids and medicinally interesting molecules has been demonstrated by the total syntheses of 8-aza-prostaglandin E 1 , 11-hydroxylated analogues of the lead compounds CP-734432 and PF-04475270, (+)-castanospermine, (+)-1-epi-castanospermine, 7-deoxy-6-epi-castanospermine as well as 9-epi-sessilifoliamide J.

show abstract

Prostaglandin E₁ causes sedation and increases 5‐hydroxytryptamine turnover in rat brain

Cited by 65 publications

References 27 publications

Modulation of seizure pattern in the rat by neutral metabolites of indoleamines

Modulation of seizure pattern in the rat by neutral metabolites of indoleamines

Suppression of pentylenetetrazol-induced seizures by hydralazine associated with 5-hydroxytryptaminergic system in rat brain.

Efficient asymmetric syntheses of alkaloids and medicinally relevant molecules based on heterocyclic chiral building blocks

Contact Info

Product

Resources

About

Prostaglandin E1 causes sedation and increases 5‐hydroxytryptamine turnover in rat brain

Cited by 65 publications

References 27 publications

Modulation of seizure pattern in the rat by neutral metabolites of indoleamines

Modulation of seizure pattern in the rat by neutral metabolites of indoleamines

Suppression of pentylenetetrazol-induced seizures by hydralazine associated with 5-hydroxytryptaminergic system in rat brain.

Efficient asymmetric syntheses of alkaloids and medicinally relevant molecules based on heterocyclic chiral building blocks

Contact Info

Product

Resources

About

Prostaglandin E₁ causes sedation and increases 5‐hydroxytryptamine turnover in rat brain