Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: CAS:110-85-0 (piperazine)
 5,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Substances with varying structural components have been shown to have 5-hydroxytryptamine (5-HT)-like properties in the CNS. In this study, putative 5-HT agonists with indoleamine moeities--lysergic acid diethylamide (LSD) and 5-methoxy-N,N-dimethyltryptamine (5-MeODMT)--and with piperazine moieties--quipazine (Quip) and 6-chloro-2-(1-piperazinyl)pyrazine (6-CPP) were administered to rats. Local cerebral glucose utilisation was measured using the [14C]2-deoxyglucose autoradiographic technique. It was found that in most cerebral structures, these substances produced dose-dependent reductions in glucose utilisation. However, Quip and 6-CPP increased glucose utilisation in specific areas of the diencephalon (e.g., nucleus reuniens) and produced a biphasic effect in some but not all extrapyramidal structures (e.g., ventromedial caudate nucleus). No such increases in local cerebral glucose utilisation were measured following LSD or 5-MeODMT administration. These results indicate that although similarities exist between the effects of indoleamine- and piperazine-containing 5-HT agonists on local cerebral glucose utilisation there are also significant differences in the overall patterns of response produced.
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PMID:Local cerebral glucose utilisation following indoleamine- and piperazine-containing 5-hydroxytryptamine agonists. 394 Feb 73

The effects of 5-carboxamide tryptamine, which activates non-5-hydroxytryptamine2-'atypical' receptors for 5-hydroxytryptamine (5-HT) in the dog saphenous vein, was studied on the complete distribution of cardiac output and common carotid blood flow in anaesthetized pigs. The drug was infused for 10 min at the rate of 0.025, 0.1 and 0.4 micrograms kg-1 min-1 either intravenously (cardiac output distribution) or intra-arterially (carotid distribution). 5-Carboxamide tryptamine decreased arterial blood pressure due to a reduction of cardiac output. This reduction was confined to its arteriovenous anastomotic component; the component used for the tissue perfusion (nutrient part) in fact increased. Similar changes were observed in the carotid blood flow distribution. Vasodilation was observed in several tissues, but the skin, ears and stomach responded most prominently. The effects of 5-carboxamide tryptamine on the carotid distribution were not significantly modified by cyproheptadine (1 mg kg-1). It is concluded that, like 5-HT, 5-carboxamide tryptamine constricts arteriovenous anastomoses and dilates arterioles by activating non-5-HT2-'atypical' receptors. These 'atypical' 5-HT receptors appear to be of the 5-HT1 type since both 5-carboxamide tryptamine and BEA 1654, a new piperazine derivative, produced similar vascular effects in the carotid bed of the pig and also showed a high and selective affinity for the 5-HT1 binding sites.
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PMID:5-Carboxamide tryptamine, a compound with high affinity for 5-hydroxytryptamine1 binding sites, dilates arterioles and constricts arteriovenous anastomoses. 397 21

Pirenperone, an antagonist of 5-HT2 but not 5-HT1 receptors, has been studied for its central antiserotonergic and antidopaminergic activity. Pirenperone (0.00525-0.1 mg/kg) antagonized dose-dependently stimulation of the hind limb flexor reflex in spinal rats induced by LSD, quipazine or fenfluramine, and hyperthermia induced by serotonin (5-hydroxytryptamine; 5-HT)-like drugs (1-5-hydroxytryptophan, fenfluramine, p-chloroamphetamine, 1-/m-chlorophenyl/-piperazine, quipazine) in heat-adapted rats. Pirenperone also counteracted tryptamine-induced convulsions in rats (ID50 = 0.87 mg/kg); however, this action was weaker than that of metergoline (ID50 = 0.22 mg/kg). Pirenperone (0.1-1.6 mg/kg) produced sedation in mice and rats, and-in doses of 0.4-6.4 mg/kg-catalepsy in rats. Given in doses ranging from 0.1 to 1.6 mg/kg, pirenperone antagonized d-amphetamine-induced locomotor hyperactivity in mice and rats, the hyperactivity induced by apomorphine in rats, apomorphine- or d-amphetamine-induced stereotypy in rats and stimulation of the hind limb flexor reflex induced by the alpha-adrenoceptor agonist-clonidine. Pirenperone (6.4 mg/kg) significantly attenuated apomorphine (1 mg/kg)-induced hypothermia in mice. The results obtained indicate that pirenperone may be regarded as a relatively specific antagonist of the 5-HT2 receptor only when it is employed in very low doses (less than 0.1 mg/kg). Used in higher doses (greater than 0.1 mg/kg), it behaves like a typical neuroleptic, i.e. like a dopamine antagonist with antiserotonergic, antitryptaminergic and antiadrenergic properties.
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PMID:Central antiserotonergic and antidopaminergic action of pirenperone, a putative 5-HT2 receptor antagonist. 404 12

At 500 micrograms-4 mg/ml piperazine and the anti-Ascaris fraction of the ethanolic extract of the bark of the erin tree (Polyadoa umbelleta) have equipotent inhibitory effects on submaximal contractions induced by equipotent doses of acetylcholine, nicotine and 5-hydroxytryptamine on the guinea-pig ileum and the rabbit duodenum. Similar inhibitory effects were noted on: acetylcholine, adrenaline, histamine, and barium chloride-induced contractions in the guinea-pig vas deferens, oxytocin and acetylcholine-induced contractions in the non-pregnant rat uterus. These actions indicate that piperazine and erin possess definite non-specific smooth muscle depressant properties. The need for the elucidation of the chemical nature of the active constituent in "erin" and for in-vivo anti-Ascaris activity studies in man is stressed.
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PMID:Effects of piperazine citrate and of the anti-Ascaris fraction of the ethanolic extract of the bark of Polyadoa umbellata (erin) on mammalian non-vascular smooth muscle. 647 82

In guinea pig brain stem preparations [3H]5-hydroxytryptamine (5HT) bound specifically to both high and low affinity sites, but specific [3H]spiperone binding was low and could not be consistently detected. This indicates a prevalence of 5HT-1 type receptors in this tissue. High affinity-specific [3H]5HT binding was more potently displaced by indole-containing 5HT agonists than by piperazine-containing 5HT agonists. This agreed with the observation that indole-containing, but not piperazine-containing compounds induced dose-dependent myoclonus in guinea pigs which originates from brain stem. The capacity of indoleamine antagonists to displace [3H]5HT-specific binding from guinea pig brain stem was similar to their reported potency in displacing [3H]5HT from 5HT-1 receptors. The [3H]5HT-labelled binding site in guinea pig brain stem is a 5HT-1 receptor and appears to be responsible for the induction of indoleamine-dependent myoclonus.
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PMID:Correlation of [3H]5-hydroxytryptamine (5HT) binding to brain stem preparations and the production and prevention of myoclonus in guinea pig by 5HT agonists and antagonists. 649 22

Recent studies indicate that there are multiple subtypes of the 5-hydroxytryptamine 1 (5-HT1) receptor. Previously, we provided evidence consistent with the finding that multiple states of the 5-HT1 receptor are present when the binding of [3H]-5-HT is measured in the absence of guanine nucleotides. When 1 mM GTP was present in the [3H]-5-HT receptor binding assay, the high affinity state was eliminated. As the presence of multiple states of a receptor complicates the interpretation of the inhibition of [3H]-5-HT binding caused by serotonin agonists and antagonists, we examined the ability of a series of these drugs to compete for 15 nM [3H]-5-HT binding in the presence of 1 mM GTP in the rat frontal cortex. Eight agonists and five antagonists showed selectivity for the two subtypes of the 5-HT1 receptor, whereas three agonists and four antagonists showed the same affinity for these two receptors subtypes. Most of the compounds examined exhibited only a modest 10- to 30-fold degree of selectivity. However, 1-(m-trifluoromethylphenyl) piperazine and 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)indole were about 65-fold selective and spiperone was over 100-fold selective for one of the receptor subtypes. The subtype specificity of the selective compounds was determined using either spiperone, a selective 5-HT 1A compound, or 1-(m-trifluoromethylphenyl)piperazine, a selective 5-HT 1B compound, to preferentially inhibit one of the receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Determination of selective and nonselective compounds for the 5-HT 1A and 5-HT 1B receptor subtypes in rat frontal cortex. 650 10

Myoclonic jerking in guinea pigs originates from the brainstem. Indole-containing 5-hydroxytryptamine (5-HT) agonists, but not piperazine-containing 5-HT agonists, induced myoclonus in guinea pigs at pharmacologically relevant doses. Guinea pig brainstem preparations possessed specific binding sites for [3H]5-HT but specific [3H]spiperone binding was low and inconsistent. 5-HT-1 receptors appear to predominate in this tissue. High affinity [3H]5-HT binding was potently displaced by indole-containing 5-HT agonists but only weakly displaced by piperazine-containing 5-HT agonists. The [3H]5-HT specific binding site in guinea pig brainstem responsible for the induction of indoleamine-dependent myoclonus has the characteristics of a 5-HT-1 receptor.
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PMID:5-Hydroxytryptamine (5-HT)-dependent myoclonus in guinea pigs is induced through brainstem 5-HT-1 receptors. 672 93

L-5-Hydroxytryptophan (5HTP) induces in guinea pigs a myoclonic jerking which is dependent upon stimulation of brainstem 5-hydroxytryptamine (5HT) receptors. We have investigated the ability of 5HT precursors and a range of synthetic 5HT agonists to produce myoclonus. The 5HT precursors and 5HT agonists containing an indole nucleus induced dose-dependent jerking in guinea pigs. In contrast, 5HT agonists possessing a piperazine moiety induced occasional jerking only at toxic doses, but not a those doses normally associated with 5HT agonist activity. The difference in activity between the indole-containing compounds and piperazine-containing 5HT agonists suggests that myoclonus is due to activation of an indole-selective brainstem 5HT receptor and provides further evidence for multiple cerebral 5HT receptors.
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PMID:Myoclonus in guniea pigs is induced by indole-containing but not piperazine-containing 5HT agonists. 708 78

In order to test the hypothesis that a 5-hydroxytryptamine (5-HT)-induced increase in vascular permeability results from a cascade triggered by activation of the synthesis of nitric oxide (NO), the vascular permeability was investigated using the Pontamine sky blue leakage method in male mice. Subcutaneous injection of 5-HT induced a dose-related increase of vascular permeability at the injection site. The vascular permeability induced by 5-HT was inhibited by pretreatment with intraperitoneal injection of ketanserin (5-HT2A antagonist) and methysergide (5-HT1/2A antagonist), less efficiently by 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl] piperazine (NAN-190) (5-HT1A antagonist), but not by granisetron (5-HT3 antagonist). Increase in vascular permeability induced by 5-HT was inhibited by concurrent intravenous administration of NO synthase inhibitors NG-nitro-L-arginine methyl ester (L-NAME) and methylene blue but not by the inactive enantiomer NG-nitro-D-arginine methyl ester (D-NAME). These results suggest that 5-HT increases vascular permeability by activating the 5-HT receptors and that endogenous NO is involved in this effect of 5-HT.
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PMID:Possible role of nitric oxide in 5-hydroxytryptamine-induced increase in vascular permeability in mouse skin. 753 Dec 92

This study investigated whether activation of serotonin1A [5-hydroxytryptamine (5-HT)1A] receptors in the dorsal horn of the spinal cord attenuates the reflex pressor response to static contraction and passive muscle stretch. In addition, we determined if the attenuation of the response to contraction is mediated by inhibiting substance P (SP) release in the dorsal horn. Static contractions of the triceps surae muscle of chloralose-anesthetized cats were induced by stimulating the cut L7 and S1 ventral roots. Microdialysis (10 mM) of a selective 5-HT1A agonist [8-hydroxy-2-(di-N-propylamino)tetralin (8-OH-DPAT)] into the L7 dorsal horn region produced a reversible attenuation of the reflex pressor response to a 1-min contraction (in mmHg: control = 36 +/- 3; 8-OH-DPAT = 17 +/- 3; recovery = 31 +/- 8; P = 0.013; n = 6) or passive stretch (in mmHg: control = 36 +/- 6; 8-OH-DPAT = 15 +/- 2; recovery = 32 +/- 6; P = 0.002; n = 6). However, a 5-HT1B agonist, 1-[3-(trifluoromethyl)-phenyl]piperazine, had no effect on the reflex pressor response. During 5-min contractions (n = 8), 8-OH-DPAT (10 mM) also blunted the pressor response but had no effect on the levels of SP-like immunoreactivity (in fmol/100 microliters: control = 0.492 +/- 0.026; 8-OH-DPAT = 0.501 +/- 0.034). These results suggest that activation of 5-HT1A receptors in the dorsal horn attenuates the reflex pressor response to contraction through a mechanism other than inhibition of SP release.
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PMID:Modulation of reflex pressor response to contraction and effect on substance P release by spinal 5-HT1A receptors. 753 69


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