In vitro studies have suggested that terguride blocks the contractile and relaxant responses produced by 5-hydroxytryptamine (5-HT) via 5-HT receptors. This study has now investigated terguride's blocking properties on central/peripheral 5-HT receptors in anaesthetized or pithed rats. Male Wistar anaesthetized/pithed rats were cannulated for recording blood pressure and heart rate and for i.
View Article and Find Full Text PDFRationale: 2-Bromoterguride, a dopamine D receptor partial agonist with antagonist properties at serotonin 5-HT receptors and α-adrenoceptors, meets the prerequisites of a putative atypical antipsychotic drug (APD). We recently showed that 2-bromoterguride is effective in tests of positive symptoms of schizophrenia in rats without inducing extrapyramidal side effects or metabolic changes.
Objective: In continuation of our recent work, we now investigated the effect of 2-bromoterguride on apomorphine and phencyclidine (PCP)-induced disruptions of prepulse inhibition (PPI) of the acoustic startle response, a measure of sensory gating.
Psychopharmacology (Berl)
August 2016
Rationale: Recently, we showed that 2-bromoterguride acted as a dopamine D2 receptor partial agonist, a serotonin 5-HT2A and α2C-adrenergic receptor antagonist, and exhibited antidopaminergic efficacy in amphetamine-induced locomotion (AIL) in rats without inducing catalepsy.
Objective: To extend our knowledge on the antipsychotic effects of 2-bromoterguride, we used convergent preclinical animal models and tests; i.e.
Extracts of the bark of willow species (Salix spp.) are popular herbal remedies to relieve fever and inflammation. The effects are attributed to salicin and structurally related phenolic metabolites, while polyphenols including procyanidins are suggested to contribute to the overall effect of willow bark.
View Article and Find Full Text PDFRationale: Almost all antipsychotic drugs (APDs), irrespective of whether they belong to the first-generation (e.g. haloperidol) or second-generation (e.
View Article and Find Full Text PDFPolyphenols including procyanidins have been reported to reduce the risk of cardiovascular diseases. However, polyphenolic extracts represent complex mixtures, and detailed information on their chemical composition is commonly lacking. The aim of this study was to investigate the potential of a highly purified and chemically defined 2,3-cis-procyanidin sample (di- to hexameric [4β,8]-linked oligomers) from Nelia meyeri to relax coronary arteries and to get insight into the underlying mechanisms.
View Article and Find Full Text PDFNaunyn Schmiedebergs Arch Pharmacol
June 2012
Enhanced pulmonary vasoconstriction in response to injuries of the central nervous system and hypoxia result in pulmonary edema due to increased sympathetic activation. This study aimed to characterize α(2)-adrenoceptor (AR)-mediated responses in porcine pulmonary arteries. α(2)-AR-mediated vasoconstriction was studied using a tissue bath protocol.
View Article and Find Full Text PDFSerotonin (5-hydroxytryptamine; 5-HT) is involved in heart valve tissue fibrosis, pulmonary arterial fibrosis, and pulmonary hypertension. We aimed at characterizing the antiserotonergic properties of the ergot alkaloid derivative terguride [1,1-diethyl-3-(6-methyl-8α-ergolinyl)urea] by using functional receptor assays and valvular interstitial cell culture. Terguride showed no vasoconstrictor effect in porcine coronary arteries (5-HT(2A) receptor bioassay) and no relaxant effect in porcine pulmonary arteries (5-HT(2B) receptor bioassay).
View Article and Find Full Text PDFFibrotic valvular heart disease (VHD) has been observed in patients with Parkinson's disease treated with dopamine receptor agonists such as pergolide and cabergoline. 5-Hydroxytryptamine(2B) receptor (5-HT(2B)R) agonism is the most likely cause, but other 5-HT receptors may also play a role in VHD. We aimed at characterizing the molecular fragment of cabergoline responsible for agonism at 5-HT(2B)R and 5-HT(2A)R.
View Article and Find Full Text PDFThe herbal drug ginger (Zingiber officinale Roscoe) may be effective for treating nausea, vomiting, and gastric hypomotility. In these conditions, cholinergic M (3) receptors and serotonergic 5-HT (3) and 5-HT (4) receptors are involved. The major chemical constituents of ginger are [6]-gingerol, [8]-gingerol, [10]-gingerol, and [6]-shogaol.
View Article and Find Full Text PDFThe isolated rat tail artery (RTA) represents an in vitro model of the cutaneous circulation. We have characterised the postjunctional α(2)-adrenoceptor subtype mediating vasoconstriction to the α(2)-adrenoceptor (α(2)-AR) agonist UK14304 in RTA. In non-precontracted arterial rings at 32°C, a physiological temperature for the RTA, UK14304 elicited only slight contractions which were markedly enhanced after precontraction with serotonin (5-HT; 10-50 nM).
View Article and Find Full Text PDFA series of phenylpiperazine derivatives of phenytoin was evaluated for their affinity at α(1)-adrenoceptor subtypes in functional bioassays (rat tail artery: α(1A) and/or α(1B); guinea pig spleen: α(1B); rat aorta: α(1D)). The most potent compounds at α(1A)-, α(1B)- and α(1D)-adrenoceptors, 11, 18 and 8, showed affinities in the submicromolar range. The role of a hydrogen bond donor group for affinity and selectivity at α(1B)-adrenoceptors, postulated by Bremner's pharmacophore model, was confirmed by functional and molecular modelling studies.
View Article and Find Full Text PDFWe have recently shown that the postjunctional alpha(2)-adrenoceptor mediating contraction of porcine pulmonary veins is of the alpha(2C)-subtype. We could also demonstrate that alpha(1)-adrenoceptors might contribute to the contraction in that blood vessel. In the present study, we aimed at characterising the alpha(1)-adrenoceptor subtype(s) involved using pharmacological and molecular biological methods.
View Article and Find Full Text PDFThe present study set out to analyse the pharmacological profile of the inhibitory responses induced by the antimigraine agents dihydroergotamine (DHE) and methysergide on the tachycardic responses to preganglionic sympathetic stimulation in pithed rats. For this purpose, 132 male Wistar normotensive rats were pithed and prepared to: (i) selectively stimulate the preganglionic (C(7)-T(1)) cardiac sympathetic outflow; or (ii) receive intravenous (i.v.
View Article and Find Full Text PDFErgotamine inhibits the sympathetically-induced tachycardia in pithed rats. The present study identified the pharmacological profile of this response. Male Wistar rats were pithed and prepared to stimulate the preganglionic (C(7)-T(1)) cardiac sympathetic outflow.
View Article and Find Full Text PDFBreast cancer development and breast cancer progression involves the deregulation of growth factors leading to uncontrolled cellular proliferation, invasion and metastasis. Transforming growth factor (TGF)-beta plays a crucial role in breast cancer because it has the potential to act as either a tumor suppressor or a pro-oncogenic chemokine. A cross-communication between the TGF-beta signaling network and estrogens has been postulated, which is important for breast tumorigenesis.
View Article and Find Full Text PDFDibenzo- and benzindolo-azecines represent a novel class of high-affinity dopamine receptor antagonists. To further characterize these drugs as potential neuroleptics, we selected a set of azecine derivatives and ring expanded homologues and we measured their antagonist activity at the 5-HT(2A) receptor in the porcine coronary artery. SARs found for the 5-HT(2A) receptor resemble those for the D1 but not the D2 receptor.
View Article and Find Full Text PDFCardiac-valve regurgitation observed in Parkinson patients treated with the ergoline dopamine receptor agonist 8beta-methylthiomethyl-6-propylergoline (pergolide) has been associated with the agonist efficacy of the drug at 5-hydroxytryptamine(2B) (5-HT(2B)) receptors. 5-HT(2A) receptors may also play a role in pergolide-induced cardiac-valve regurgitation. We studied the pharmacological profile of pergolide and eight derivatives in porcine vascular rings endowed with 5-HT(2B) and 5-HT(2A) receptors to detect the molecular fragment of the pergolide molecule that may be responsible for agonism at these receptors.
View Article and Find Full Text PDFNaunyn Schmiedebergs Arch Pharmacol
January 2008
Ergot alkaloids act as (partial) agonists or antagonists at serotonergic, dopaminergic and alpha-adrenergic receptors. In contrast to their affinity at serotonergic (5-HT) and dopaminergic receptor subtypes, only limited information is available concerning their interaction with alpha-adrenoceptor subtypes. This especially holds true for native alpha-adrenoceptors.
View Article and Find Full Text PDFN,N'-Dialkyl-1,2-bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamines show structural analogy with estrogens and selective estrogen receptor modulators. Because the vasodilator properties of these compounds are unknown, we investigated their potential to relax porcine coronary arteries and determined the mechanism(s) of relaxation. Isolated porcine coronary arterial rings were suspended in organ chambers, precontracted with KCl (30 mM), and the relaxant response was determined by measurement of changes in isometric force.
View Article and Find Full Text PDFIt has been suggested that the alpha(2)-adrenoceptors mediating cardiac sympatho-inhibition in pithed rats closely resemble the pharmacological profile of the alpha(2A)-adrenoceptor subtype. However, several lines of evidence suggest that more than one subtype may be involved. Thus, the present study has pharmacologically re-evaluated the receptor subtype(s) involved in the inhibitory effect of the alpha(2)-adrenoceptor agonist, B-HT 933, on the tachycardic responses elicited by selective cardiac sympathetic stimulation (0.
View Article and Find Full Text PDFNaunyn Schmiedebergs Arch Pharmacol
December 2006
This study has characterised the pharmacological profile of some dopaminergic agents of the ergoline family including the antiparkinsonian drug 8S-lisuride at native guinea pig histamine H(1) receptors and recombinant human and guinea pig H(1) receptors. We used segments of guinea pig ileum to study contractile responses, Sf9 insect cell membranes expressing the guinea pig H(1) receptor (gpH(1)R) and the human H(1) receptor (hH(1)R) to analyse GTPase activity of G(q)-proteins and we conducted [(3)H]mepyramine binding studies using recombinant gpH(1)Rs and hH(1)Rs. 8S-Lisuride acted as a potent partial agonist at H(1)Rs of guinea pig ileum (pD(2) 7.
View Article and Find Full Text PDFTwo 3alpha-acyloxytropanes with unique monoterpenoic acyl moieties, bonabiline A and its anhydro derivative bonabiline B, have been isolated from the roots of Bonamia spectabilis. Their structures were elucidated by detailed spectroscopic analysis. Due to the structural similarity of bonabiline A to atropine/hyoscyamine, the affinity of both bonabilines to the muscarinic M (3) receptor was studied in the isolated guinea-pig ileum.
View Article and Find Full Text PDFThe present study characterises the vasorelaxant response to raloxifene in isolated rings of porcine coronary artery. Tissues precontracted either with KCl (30 mM) or prostaglandin F(2alpha) (PGF(2alpha); 3 microM) were concentration-dependently relaxed by raloxifene (0.1-10 microM).
View Article and Find Full Text PDFRestrictive cardiac valvulopathies observed in Parkinson patients treated with the ergoline dopamine agonist pergolide have recently been associated with the agonist efficacy of the drug at 5-hydroxytryptamine2B (5-HT2B) receptors. To evaluate whether agonism at 5-HT2B receptors is a phenomenon of the class of the ergolines, we studied 5-HT2B receptor-mediated relaxation in porcine pulmonary arteries to five ergolines which are used as antiparkinsonian drugs. Pergolide and cabergoline were potent full agonists in this tissue (pEC50 8.
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