Diazabicyclononanones, a potent class of kappa opioid analgesics

Holzgrabe, Ulrike; Cambareri, A.; Kuhl, Ulrich; Siener, Tom; Brandt, Wolfgang; Straßburger, W.; Friderichs, Elmar; Englberger, Werner; Kögel, Babette; Haurand, Michael

doi:10.1016/s0014-827x(02)01243-0

Cited by 8 publications

(4 citation statements)

References 13 publications

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“…142 In 2002, Holzgrabe and coworkers found that ketazocine was ~2.5-3 times more selective towards KOR than MOR or DOR (Ki for KOR = 0.21 nM, Ki for MOR = 0.6 nM, Ki for DOR = 0.5 nM). 143 The activity of ketazocine is lowest on DOR, which is consistent with other benzomorphans as benzomorphans often have lower activities on DOR than on KOR and/or MOR. 144 Due to its higher preference for KOR than MOR, ketocyclazocine produced antinociceptive effects but avoided substantial addiction liability and severe respiratory depression, 141 which are common concerning characteristics of potent MOR agonists like morphine.…”

Section: Iii2 Pentazocinesupporting

confidence: 67%

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A systematic review on the kappa opioid receptor and its ligands: New directions for the treatment of pain, anxiety, depression, and drug abuse

Khan

Sawyer

Akins

et al. 2022

European Journal of Medicinal Chemistry

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Section: Iii2 Pentazocinesupporting

confidence: 67%

“…However, ketazocine is not devoid of all adverse side effects; at dosages that elicited antinociception in rats, sedation and diuresis were also observed. 143…”

Section: Iii2 Pentazocinementioning

confidence: 99%

A systematic review on the kappa opioid receptor and its ligands: New directions for the treatment of pain, anxiety, depression, and drug abuse

Khan

Sawyer

Akins

et al. 2022

European Journal of Medicinal Chemistry

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“…Neither the patient experienced opioid‐specific side effects, withdrawal symptoms, drug abuse, or problems in switching to a different strong opioid 46,47 . With respect to the receptor kinetics, the switch from one opioid to another is not associated with a refractory period between the end of buprenorphine action and the beginning of the new analgesic's effect 48 …”

Section: Discussionmentioning

confidence: 99%

Transdermal Buprenorphine for Central Neuropathic Pain: Clinical Reports

Guetti

Angeletti²,

Marinangeli

et al. 2010

Pain Practice

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Transdermal buprenorphine is an effective analgesic for a variety of pain conditions. Traditionally, neuropathic pain is treated with medications such as tricyclic antidepressants or anticonvulsants, with opioid medications as second or third-line agents. We present two different painful conditions of presumed neuropathic origin, with complex etiopathogenesis, which were successfully treated with buprenorphine. The results of treatment of these neuropathic pain syndromes with buprenorphine are encouraging, suggesting that it might represent a valid alternative to standard approaches for central neuropathic pain.

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“…Several heterocyclic bicyclo[3.3.1]nonan-9-ones were found to have a high affinity to κ-opioid receptors [6,7], and some of them showed a reasonable κ-agonistic activity in the mouse vas deferens test [13]. In addition, these compounds were characterized by long duration of action and high oral bioavailability [14]. Although these compounds bear at least one positive charge under physiological conditions they showed a considerable lipophilicity, indicating the possibility of passing the blood-brain barrier [16].…”

Section: Discussionmentioning

confidence: 99%

Kappa-receptor selective binding of opioid ligands with a heterocyclic bicyclo[3.3.1]nonan-9-one structure

Benyhe¹,

Márki²,

Nachtsheim³

et al. 2003

Acta Biologica Hungarica

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Previous pharmacological results have suggested that members of the heterocyclic bicyclo[3.3.1]nonan-9-one-like compounds are potent kappa-opioid receptor specific agonists. One lead molecule of this series. called compound 1 (dimethyl 7-methyl-2,4-di-2-pyridyl-3.7-diazabicyclo[3.3.1]nonan-9-one-1,5-dicarboxylate) exhibited high affinity for [3H]ethylketocyclazocine and [3H]U-69.593 binding sites in guinea pig cerebellar membranes which known to be a good source for kappa1 receptors. It was shown by molecular modelling that heterocyclic bicyclo[3.3.1]nonan-9-ones fit very well with the structure of ketazocine, a prototypic kappa-selective benzomorphan compound; when compared to the arylacetamide structure of U-69.593, a specific kappa1-receptor agonist, a similar geometry was found with a slightly different distribution of the charges. It is postulated, that the essential structural skeleton involved in the opioid activity is an aryl-propyl-amine element distributed along the N7-C6-C5-C4-aryl bonds.

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Diazabicyclononanones, a potent class of kappa opioid analgesics

Cited by 8 publications

References 13 publications

A systematic review on the kappa opioid receptor and its ligands: New directions for the treatment of pain, anxiety, depression, and drug abuse

A systematic review on the kappa opioid receptor and its ligands: New directions for the treatment of pain, anxiety, depression, and drug abuse

Transdermal Buprenorphine for Central Neuropathic Pain: Clinical Reports

Kappa-receptor selective binding of opioid ligands with a heterocyclic bicyclo[3.3.1]nonan-9-one structure

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