Involvement of α2-adrenoceptors in the cardiovascular effects of moxonidine

Urban, Rolf; Szabó, Béla; Starke, Klaus

doi:10.1016/0014-2999(95)00297-x

Cited by 40 publications

(35 citation statements)

References 28 publications

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“…To determine if the above actions were because of actions at a2ARs, we studied the effect of UK14304, a specific a2-adrenoreceptor agonist with an I1 binding site/a2 binding site affinity ratio o0.01 (Andorn et al, 1988;Bricca et al, 1993;Buccafusco et al, 1995;Urban et al, 1995). In contrast to the effects observed in morphine-dependent rats pretreated with clonidine, administration of UK14304 (0.1 mg/kg i.v.)…”

Section: Costimulation Of A2-adrenergic Receptors and I1rs Is Requirementioning

confidence: 99%

Prolonged Activation of Mesolimbic Dopaminergic Neurons by Morphine Withdrawal Following Clonidine: Participation of Imidazoline and Norepinephrine Receptors

Georges

Aston‐Jones

2003

Neuropsychopharmacol

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The a2 adrenoceptor (a2R) agonist clonidine is used as a treatment for heroin addiction. Substantial evidence indicates that dopaminergic and noradrenergic systems have key roles in opiate dependence and withdrawal but the possible interactions between these two pathways remain unclear. The objective of this study was to establish the effects of clonidine pretreatment on ventral tegmental area dopaminergic (VTA DA) neuronal activity during morphine withdrawal. Responses of VTA DA neurons to withdrawal precipitated by naltrexone were characterized in anesthetized rats using extracellular recordings. As expected, withdrawal produced a marked inhibition of VTA DA neuronal activity. However, pretreatment with clonidine prevented this inhibition induced by withdrawal, and instead produced a long-lasting activation of firing rate (+50%) and burst firing (+19%). In contrast, pretreatment with a more selective a2R agonist, UK14304, did not prevent the inhibition of VTA DA neuron activity during withdrawal. We tested whether the high affinity of clonidine for imidazoline-1 receptors (I1Rs) was responsible for the difference between these two a2R agonists. In morphine-dependent rats pretreated with rilmenidine (mixed a2R/I1R agonist), precipitation of withdrawal elicited a 22% increase of VTA DA impulse activity. The action of clonidine on I1Rs was studied by coadministering clonidine with RX821002, a specific a2R antagonist. Pretreatment with RX821002 plus clonidine prevented the inhibition of VTA DA activity during withdrawal but failed to produce excitation. These results indicate that the pharmacological effects of clonidine on VTA DA neurons during morphine withdrawal is related to actions on I1Rs as well as a2Rs.

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Section: Costimulation Of A2-adrenergic Receptors and I1rs Is Requirementioning

confidence: 99%

Prolonged Activation of Mesolimbic Dopaminergic Neurons by Morphine Withdrawal Following Clonidine: Participation of Imidazoline and Norepinephrine Receptors

Georges

Aston‐Jones

2003

Neuropsychopharmacol

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“…Furthermore, the central hypotensive effect of both agents can be antagonized by the selective I-receptor antagonists efaroxan and idazoxan [58][59][60]. The involvement of I 1 -receptors in the effects of both compounds has been contested, however, by Urban et al [61,62], who concluded from their experiments that the effects both of moxonidine and of rilmenidine predominantly involve central ␣ 2 -adrenoceptors. An interaction between I 1 -and ␣ 2 -adrenoceptors in the CNS, involving the contribution of both receptor types, may be considered as well [63].…”

Section: Pharmacological Characteristics Of Moxonidine and Rilmenidinementioning

confidence: 99%

Central imidazoline (I1) receptors as targets of centrally acting antihypertensives

Zwieten

1997

Journal of Hypertension

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“…3), confirming that central administration of a 2 antagonists could elicit hypertension and tachycardia. Clonidine induced hypotension by stimulating central presynaptic a 2 -autoreceptors; it was able to induce bradycardia by activating peripheral cardiac presynaptic a 2 -autoreceptors [Urban et al, 1995]. Intracisternally injected Eu-A, Eu-B, or Eu-C at a 0.03 mM inhibited clonidine-induced hypotension but not clonidine-induced bradycardia.…”

Section: Discussionmentioning

confidence: 99%

Structure–activity relationships of isoeugenol‐based chlorophenylpiperazine derivatives on serotonergic/adrenergic receptor, platelet aggregation, and lipid peroxidation

Shen

Chang

Lin

et al. 2010

Drug Development Research

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Three isoeugenol-based eugenosedin chlorphenylpiperazine derivatives, Eu-A, Eu-B, and Eu-C, were synthesized and tested for their serotonergic, adrenergic antagonist, antioxidant, and antiaggregation activities. In radioligand binding assays, all three agents displayed significant binding affinities on a 1 , a 2 , b 1 , 5-HT 1B , and 5-HT 2A receptors. In human platelet, they inhibited epinephrine and 5-HTinduced aggregation, and in human platelet with a 2 and 5-HT 2A receptors they had a competitive binding effect. Eu-B and Eu-C were more potent than Eu-A. All compounds had antioxidant effects derived from aryloxypropanolamine. Eu-A, Eu-B, or Eu-C (1, 3, 5 mg/kg iv) given to normotensive Wistar rats produced a dose-dependent decrease in mean arterial blood pressure and heart rate and when injected into the cisternum, Eu-A, Eu-B, or Eu-C (0.3, 0.03 mmol) increased blood pressure within 15 min. Pretreatment with any of the three agents inhibited clonidine (38 pmol)-induced hypotension. In vitro experiments, Eu-A, Eu-B, or Eu-C (1, 10, and 100 mM) competitively antagonized norepinephrine-, clonidine-, and 5-HT (10 À8 -10 À4 M)-induced vasocontraction in isolated rat aorta, and competitively antagonized isoproterenol (10 À8 -10 À4 M)-induced positive inotropic effects in a concentration-dependent manner in the isolated rat left atrium. In isolated rabbit ear arteries sensitized with 16 mM K 1 , all three agents antagonized 5-nonyloxytryptamine-and 5-HT-induced vasocontractions. These findings show that Eu-A, Eu-B, and Eu-C possess functional a 1 , a 2 , b 1 , 5-HT 1B , and 5-HT 2A receptor blocking activities. In conclusion, the changes in the position of chloride at phenylpiperazine influenced the serotonergic receptor, adrenoceptor DDR Published online in Wiley InterScience (www.interscience.wiley. com).

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Involvement of α2-adrenoceptors in the cardiovascular effects of moxonidine

Cited by 40 publications

References 28 publications

Prolonged Activation of Mesolimbic Dopaminergic Neurons by Morphine Withdrawal Following Clonidine: Participation of Imidazoline and Norepinephrine Receptors

Prolonged Activation of Mesolimbic Dopaminergic Neurons by Morphine Withdrawal Following Clonidine: Participation of Imidazoline and Norepinephrine Receptors

Central imidazoline (I1) receptors as targets of centrally acting antihypertensives

Structure–activity relationships of isoeugenol‐based chlorophenylpiperazine derivatives on serotonergic/adrenergic receptor, platelet aggregation, and lipid peroxidation

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