Absence of opiate and histamine H2 receptor–mediated effects of Clonidine

Watkins, John; FitzGerald, Garret A.; Zamboulis, C.; Brown, Morris J.; Dollery, C. T.

doi:10.1038/clpt.1980.210

Cited by 46 publications

(13 citation statements)

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“…Activation of alpha-2 adrenoceptors inhibits water secretion and increases net absorption in the large bowel; this is the mechanism by which clonidine has been used to successfully treat diarrhoea [97]. Stimulation of alpha-2 adrenoceptors is known to reduce salivary secretions and may lead to a dry mouth [98].…”

Section: Neuroendocrine System Effectsmentioning

confidence: 99%

Alpha‐2 and imidazoline receptor agonistsTheir pharmacology and therapeutic role

Khan¹,

Ferguson²,

Jones³

1999

Anaesthesia

598

423

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SummaryClonidine has proved to be a clinically useful adjunct in clinical anaesthetic practice as well as in chronic pain therapy because it has both anaesthetic and analgesic-sparing activity. The more selective alpha-2 adrenoceptor agonists, dexmedetomidine and mivazerol, may also have a role in providing haemodynamic stability in patients who are at risk of peri-operative ischaemia. The side-effects of hypotension and bradycardia have limited the routine use of alpha-2 adrenoceptor agonists. Investigations into the molecular pharmacology of alpha-2 adrenoceptors have elucidated their role in the control of wakefulness, blood pressure and antinociception. We discuss the pharmacology of alpha-2 adrenoceptors and their therapeutic role in this review.

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Section: Neuroendocrine System Effectsmentioning

confidence: 99%

Alpha‐2 and imidazoline receptor agonistsTheir pharmacology and therapeutic role

Khan¹,

Ferguson²,

Jones³

1999

Anaesthesia

598

423

View full text Add to dashboard Cite

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“…For example, clonidine has been reported to have antinocicep tive effects [25,40] and to reverse opiate withdrawal symptoms [17]. Opiate receptor antagonists have been observed to block cardiovascular effects of clonidine and a-methyldopa in spontaneously hypertensive rats [13,14,27,29], but naloxone does not antagonize the cardiovascular effects of clonidine in normotensive Wistar-Kyoto rats [14,20], in normotensive humans [41], or in humans with essential hypertension [33]. In our study, naloxone did not antagonize the effects of clonidine on copulatory behavior or erectile function in normal Long-Evans rats.…”

Section: Discussionmentioning

confidence: 99%

Clonidine Suppresses Copulatory Behavior and Erectile Reflexes in Male Rats: Lack of Effect of Naloxone Pretreatment

Clark

Smith

1990

Neuroendocrinology

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Adrenergic transmitters and opioid peptides are implicated in the regulation of male sexual behavior. In the present studies we examine a possible interaction between these two neurochemical systems in the regulation of components of male sexual behavior. In mating tests, clonidine (0.25 mg/kg, 6 min pretest) induced a profound deficit in intromissive and ejaculatory behavior whereas naloxone (5 mg/kg, 20 min pretest) evinced a facilitation of ejaculatory behavior, evidenced by decreases in the ejaculation latency in the initial copulatory series and by decreases in ejaculation latency and intercopulatory interval in the second copulatory series. Importantly, prior treatment with naloxone did not prevent or attenuate the copulatory suppression induced by clonidine. In ex copula penile reflex tests, clonidine (0.25 mg/kg, 6 min pretest) decreased the incidence of seminal emission and the number of penile responses (erections, cups and flips). Naloxone (5 mg/kg, 20 min pretest) was without effect on any of the parameters of penile reflex activity and, further, failed to prevent or attenuate the erectile suppression induced by clonidine. A final study evaluated the dose-response relationship of clonidine-induced erectile dysfunction. A similar degree of erectile dysfunction was observed after 0.005, 0.025 or 0.25 mg/kg clonidine, whereas 0.0005 mg/kg was without effect. Previous studies demonstrated a dose-dependent inhibition of mounting, intromissive and ejaculatory behavior, with 0.25 mg/kg selectively eliminating ejaculatory behavior in mating tests. These data demonstrate a dose-dependent inhibition of penile reflexes, with inhibition occurring at doses lower than those required to induce copulatory dysfunction. Further, we suggest that opioid receptors sensitive to naloxone blockade are not involved in the clonidine-induced suppression of copulatory or erectile function.

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“…Symptome wie Mundtrockenheit, Hemmung der Magensaftsekretion und Obstipation nach aadrenerger Stimulation sind auf eine Hemmung der Acetylcholinfreisetzung an cholinergen Nervenendigungen zurückzuführen (108 …”

Section: Gastrointestinaltraktunclassified

Alpha₂-Agonisten in Anästhesie und Intensivmedizin

Bischoff

Kochs²

1993

Anästhesiol Intensivmed Notfallmed Schmerzther

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The neurotransmitters adrenaline and noradrenaline are non-selective adrenergic agonists which interact with both subtypes of alpha- and beta-receptors. Clonidine, an alpha 2-adrenergic drug with a selectivity ratio of 200/1 for alpha 2/alpha 1 has been used in clinical practice for more than 20 years. Although alpha 2-agonists have vasoconstrictor properties, sympatholytic effects on the central nervous system predominate. As a result, the sympathetic outflow from the medullary pressor centres is decreased mediating the hypotensive effects of the alpha 2-agonists. These compounds also exhibit sedative, anxiolytic, analgesic, and haemodynamic stabilising properties. The identification of alpha 2-adrenoceptors has yielded information on their biochemical properties, signal transduction, modulation of the sympathetic nervous system and neurotransmission. The classification of alpha 2-receptors based on anatomical locations and identified as presynaptic alpha 2-receptors and postsynaptic alpha 1-receptors proved to be untenable after postsynaptic and extrasynaptic alpha 2-receptor locations had been identified. At least 3 isoreceptors which are heterologously distributed in the brain have been identified. Guanine nucleotide proteins (G proteins) couple the receptor to an effector mechanism (i.e. intracellular messenger cascade, ion channel). More selective for the alpha 2-adrenoceptor than clonidine is dexmedetomidine (1600/1 of alpha 2/alpha 1), a very potent agonist at the alpha 2-adrenoceptor. Imidazole derivatives (like clonidine and dexmedetomidine) also bind to other nonadrenergic receptors ("imidazoline receptors") which may produce some effects (i.e. vagotonia) previously ascribed to alpha 2-adrenoceptors. alpha 2-receptors exist in brain tissue and several peripheral organs and tissues including the liver, eye, kidney, pancreas and platelets. Anaesthetic interest has focussed on reductions in anaesthetic requirements since experimental and clinical studies have shown that alpha 2-agonists expert powerful analgesic and anaesthetic effects. The hypnotic response is probably mediated by activation of alpha 2-adrenoceptors in the locus coeruleus. Analgesia is induced by modulation of the nociceptive pathway at the level of the dorsal root neuron and other sites not yet unambiguously characterised. Dexmedetomidine reduces the anaesthetic requirements for halothane by more than 90%. Cerebral blood flow and intraocular pressure are reduced by alpha 2-agonists. Epidural, intrathecal, intravenous and transdermal application of clonidine resulted in pain reduction, during and following surgery and in patients with neurogenic or otherwise intractable cancer pain. Administration of alpha 2-agonists induces only minor respiratory effects. Salivary flow is reduced by alpha 2-agonists and gastric and small-bowel motility is decreased.(ABSTRACT TRUNCATED AT 400 WORDS)

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Absence of opiate and histamine H2 receptor–mediated effects of Clonidine

Cited by 46 publications

References 0 publications

Alpha‐2 and imidazoline receptor agonistsTheir pharmacology and therapeutic role

Alpha‐2 and imidazoline receptor agonistsTheir pharmacology and therapeutic role

Clonidine Suppresses Copulatory Behavior and Erectile Reflexes in Male Rats: Lack of Effect of Naloxone Pretreatment

Alpha₂-Agonisten in Anästhesie und Intensivmedizin

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Absence of opiate and histamine H2 receptor–mediated effects of Clonidine

Cited by 46 publications

References 0 publications

Alpha‐2 and imidazoline receptor agonistsTheir pharmacology and therapeutic role

Alpha‐2 and imidazoline receptor agonistsTheir pharmacology and therapeutic role

Clonidine Suppresses Copulatory Behavior and Erectile Reflexes in Male Rats: Lack of Effect of Naloxone Pretreatment

Alpha2-Agonisten in Anästhesie und Intensivmedizin

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Alpha₂-Agonisten in Anästhesie und Intensivmedizin