Synthesis and biological evaluation of 14-alkoxymorphinans. 2. (-)-N-(Cyclopropylmethyl)-4,14-dimethoxymorphinan-6-one, a selective .mu. opioid receptor antagonist

Schmidhammer, Helmut; Burkard, W. P.; Eggstein-Aeppli, Lislott; Smith, C. F. C.

doi:10.1021/jm00122a021

Cited by 86 publications

(49 citation statements)

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“…The dose-effect curve for P-endorphin was shifted to the right in the presence of the non-selective opioid antagonist naloxone (200 nM), having an apparent K, for naloxone of 26.0 ± 4.3 nM, indicative of an action at b-opioid receptors (Figure 3). This was confirmed by the effectiveness of the b-opioid receptor selective antagonist naltrindole (Rogers et al, 1990) in antagonizing the P-endorphin response, affording a K, of 0.86±0.10nM, and the lack of antagonism by cyprodime, a selective 1i-opioid antagonist (Schmidhammer et al, 1989), affording a K> 300 nM (Figure 3). …”

Section: Mouse Vas Deferensmentioning

confidence: 65%

Evidence for lack of modulation of μ‐opioid agonist action by δ‐opioid agonists in the mouse vas deferens and guinea‐pig ileum

Elliott¹,

Traynor²

1995

British J Pharmacology

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Section: Mouse Vas Deferensmentioning

confidence: 65%

Evidence for lack of modulation of μ‐opioid agonist action by δ‐opioid agonists in the mouse vas deferens and guinea‐pig ileum

Elliott¹,

Traynor²

1995

British J Pharmacology

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“…Although it is impossible to assess the potential impact of these indirect influences on the results, it is still clear that activation of ORs is the major mechanism The prominent effects of cyprodime on the TNS-induced increase in bladder capacity indicate that activation of m ORs is essential for eliciting inhibition. The effect of cyprodime is similar to the effect of naloxone , which exhibits a 7-fold selectivity for m ORs over k ORs and 12-fold selectivity for m ORs over d ORs (Schmidhammer et al, 1989;Goodman et al, 2007). Cyprodime has a much higher m receptor selectivity than naloxone (m/k 5 28, m/d 5 110) (Schmidhammer et al, 1989), but like naloxone it has a similar low nanomolar affinity for binding to ORs in rat brain homogenates (Márki et al, 1999).…”

Section: Discussionmentioning

confidence: 79%

“…The effect of cyprodime is similar to the effect of naloxone , which exhibits a 7-fold selectivity for m ORs over k ORs and 12-fold selectivity for m ORs over d ORs (Schmidhammer et al, 1989;Goodman et al, 2007). Cyprodime has a much higher m receptor selectivity than naloxone (m/k 5 28, m/d 5 110) (Schmidhammer et al, 1989), but like naloxone it has a similar low nanomolar affinity for binding to ORs in rat brain homogenates (Márki et al, 1999). The doseresponse curve of cyprodime showing suppression of TNS inhibition (Fig.…”

Section: Discussionmentioning

confidence: 82%

Role of µ, κ, and δ Opioid Receptors in Tibial Inhibition of Bladder Overactivity in Cats

Zhang

Slater

Ferroni

et al. 2015

J Pharmacol Exp Ther

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In a-chloralose anesthetized cats, we examined the role of opioid receptor (OR) subtypes (m, k, and d) in tibial nerve stimulation (TNS)-induced inhibition of bladder overactivity elicited by intravesical infusion of 0.25% acetic acid (AA). The sensitivity of TNS inhibition to cumulative i.v. doses of selective OR antagonists (cyprodime for m, nor-binaltorphimine for k, or naltrindole for d ORs) was tested. Naloxone (1 mg/kg, i.v., an antagonist for m, k, and d ORs) was administered at the end of each experiment. AA caused bladder overactivity and significantly (P , 0.01) reduced bladder capacity to 21.1% 6 2.6% of the saline control. TNS at 2 or 4 times threshold (T) intensity for inducing toe movement significantly (P , 0.01) restored bladder capacity to 52.9% 6 3.6% or 57.4% 6 4.6% of control, respectively. Cyprodime (0.3-1.0 mg/kg) completely removed TNS inhibition without changing AA control capacity. Nor-binaltorphimine (3-10 mg/kg) also completely reversed TNS inhibition and significantly (P , 0.05) increased AA control capacity. Naltrindole (1-10 mg/kg) reduced (P , 0.05) TNS inhibition but significantly (P , 0.05) increased AA control capacity. Naloxone (1 mg/kg) had no effect in cyprodime pretreated cats, but it reversed the nor-binaltorphimine-induced increase in bladder capacity and eliminated the TNS inhibition remaining in naltrindole pretreated cats. These results indicate a major role of m and k ORs in TNS inhibition, whereas d ORs play a minor role. Meanwhile, k and d ORs also have an excitatory role in irritation-induced bladder overactivity.

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“…Naloxone preferentially blocks -opioid receptors but also has affinity for the other opioid receptor subtypes (Schmidhammer et al, 1989;Eguchi, 2004). To study the involvement of ␦-and/or -opioid receptors in amphetamine-induced inhibitory control deficits, the effects of amphetamine alone and in combination with naltrindole and nor-BNI, representing selective ␦-or -opioid receptor antagonists, respectively, were tested in the 5-CSRTT.…”

Section: Effects Of Naltrindole and Nor-bni On Amphetamine-induced Immentioning

confidence: 99%

μ-Opioid Receptors in the Nucleus Accumbens Shell Region Mediate the Effects of Amphetamine on Inhibitory Control But Not Impulsive Choice

Wiskerke

Schetters

Es³

et al. 2011

J. Neurosci.

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Acute challenges with psychostimulants such as amphetamine affect impulsive behavior in both animals and humans. With regard to amphetamine, it is important to unravel how this drug affects impulsivity since it is not only a widely abused recreational drug but also regularly prescribed to ameliorate maladaptive impulsivity. Therefore, we studied the effects of amphetamine in two rat models of impulsivity, the five-choice serial reaction time task and the delayed-reward task, providing measures of inhibitory control and impulsive choice, respectively. We focused on the role of opioid receptor activation in amphetamine-induced impulsivity as there is ample evidence indicating an important role for endogenous opioids in several behavioral and neurochemical effects of amphetamine. Results showed that amphetamine-induced inhibitory control deficits were dose-dependently attenuated by the preferential -opioid receptor antagonist naloxone, but not by the selective ␦-opioid receptor antagonist naltrindole or -opioid receptor antagonist nor-BNI (norbinaltorphimine dihydrochloride). In contrast, naloxone did not affect amphetamine-induced improvements in impulsive decision making. Naloxone also completely prevented inhibitory control deficits induced by GBR -ol]-enkephalin acetate salt) revealed that -opioid receptor activation in the shell rather than the core subregion of the nucleus accumbens (NAc) modulates inhibitory control and subserves the effect of amphetamine thereon. Together, these results indicate an important role for NAc shell -opioid receptors in the regulation of inhibitory control, probably via an interaction between these receptors and the mesolimbic dopamine system.

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Synthesis and biological evaluation of 14-alkoxymorphinans. 2. (-)-N-(Cyclopropylmethyl)-4,14-dimethoxymorphinan-6-one, a selective .mu. opioid receptor antagonist

Cited by 86 publications

References 0 publications

Evidence for lack of modulation of μ‐opioid agonist action by δ‐opioid agonists in the mouse vas deferens and guinea‐pig ileum

Evidence for lack of modulation of μ‐opioid agonist action by δ‐opioid agonists in the mouse vas deferens and guinea‐pig ileum

Role of µ, κ, and δ Opioid Receptors in Tibial Inhibition of Bladder Overactivity in Cats

μ-Opioid Receptors in the Nucleus Accumbens Shell Region Mediate the Effects of Amphetamine on Inhibitory Control But Not Impulsive Choice

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