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Cited by 67Cannabis and Cannabinoid ResearchPain Mechanisms and TreatmentsAdenosine and Purinergic Signaling

3-[2-Cyano-3-(trifluoromethyl)phenoxy]phenyl-4,4,4-trifluoro-1-butanesulfonate (BAY 59-3074): A Novel Cannabinoid CB1/CB2 Receptor Partial Agonist with Antihyperalgesic and Antiallodynic Effects

De Vry, Jean, Denzer, Dirk, Reissmueller, Elke, Eijckenboom, Maud, Heil, Markus, Meier, Heinrich, Mauler, Frank·2004·The Journal of Pharmacology and Experimental Therapeutics
DOI 10.1124/jpet.103.062836
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Abstract

3-[2-Cyano-3-(trifluoromethyl)phenoxy]phenyl-4,4,4-trifluoro-1-butanesulfonate (BAY 59-3074) is a novel, selective cannabinoid CB(1)/CB(2) receptor ligand (K(i) = 55.4, 48.3, and 45.5 nM at rat and human cannabinoid CB(1) and human CB(2) receptors, respectively), with partial agonist properties at these receptors in guanosine 5-[gamma(35)S]-thiophosphate triethyl-ammonium salt ([(35)S]GTPgammaS) binding assays. In rats, generalization of BAY 59-3074 to the cue induced by the cannabinoid CB(1) receptor agonist (-)-(R)-3-(2-hydroxymethylindanyl-4-oxy)phenyl-4,4,4-trifluoro-1-butanesulfonate (BAY 38-7271) in a drug discrimination procedure, as well as its hypothermic and analgesic effects in a hot plate assay, were blocked by the cannabinoid CB(1) receptor antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide hydrochloride (SR 141716A). BAY 59-3074 (0.3-3 mg/kg, p.o.) induced antihyperalgesic and antiallodynic effects against thermal or mechanical stimuli in rat models of chronic neuropathic (chronic constriction injury, spared nerve injury, tibial nerve injury, and spinal nerve ligation models) and inflammatory pain (carrageenan and complete Freund's adjuvant models). Antiallodynic efficacy of BAY 59-3074 (1 mg/kg, p.o.) in the spared nerve injury model was maintained after 2 weeks of daily administration. However, tolerance developed rapidly (within 5 days) for cannabinoid-related side effects, which occur at doses above 1 mg/kg (e.g., hypothermia). Uptitration from 1 to 32 mg/kg p.o. (doubling of daily dose every 4th day) prevented the occurrence of such side effects, whereas antihyperalgesic and antiallodynic efficacy was maintained/increased. No withdrawal symptoms were seen after abrupt withdrawal following 14 daily applications of 1 to 10 mg/kg p.o. It is concluded that BAY 59-3074 may offer a valuable therapeutic approach to treat diverse chronic pain conditions.

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Crossref · 10.1124/jpet.103.062836

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  • All studies with the exception of one indicated the presence of thermal hyperalgesia when animals were tested after spinal nerve ligation.

    “All studies with the exception of one78 indicated the presence of thermal hyperalgesia when animals were tested.”

    From Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside (2009) · cites this paper as [78]

  • Systemic BAY 59-3074 attenuated both mechanical allodynia and thermal hyperalgesia in the tibial nerve injury model, although pharmacological specificity was not assessed.

    “Systemic BAY 59-3074 was shown to attenuate both forms of neuropathic nociception, although pharmacological specificity was not assessed.78”

    From Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside (2009) · cites this paper as [78]

  • In the SNI model, chronic BAY 59-3074 dose escalation produces rapid tolerance to side-effects such as hypothermia but no loss in analgesic efficacy.

    “A dose-escalation study with BAY 59-3074 in the SNI model indicated that tolerance rapidly develops to side-effects observed following chronic administration (e.g. hypothermia), whereas no loss in analgesic efficacy was observed.78”

    From Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside (2009) · cites this paper as [78]

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Authors
De Vry, J., Denzer, D., Reissmueller, E., Eijckenboom, M., Heil, M., Meier, H., & Mauler, F.
Venue
The Journal of Pharmacology and Experimental Therapeutics
Publisher
Elsevier BV
Published
2004-08
Volume
310
Issue
2
Pages
620-632
ISSN
0022-3565 (ISSN-L)
DOI
10.1124/jpet.103.062836
OpenAlex
W2117833691
Cited by
63
References
42
Citations by year
2026: 1 · 2025: 1 · 2024: 2 · 2023: 1 · 2022: 2 · 2021: 1 · 2020: 3 · 2019: 2 · 2018: 2 · 2017: 3 · 2016: 2 · 2015: 2 · 2014: 4 · 2013: 3 · 2012: 2
FWCI
3.97
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Journal of Pharmacology and Experimental Therapeutics (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
  • Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
Keywords
CB1 receptor, CB2 receptor, partial agonists, antihyperalgesia, antiallodynic effect, neuropathic pain, inflammatory pain, chronic constriction injury, spared nerve injury, tibial nerve injury, spinal nerve ligation, carrageenan, complete Freund's adjuvant, drug discrimination, hypothermic effect, analgesia
MeSH terms
Alkanesulfonates, Animals, Cannabinoids, Dose-Response Relationship, Drug, Humans, Hyperalgesia, Male, Nitriles, Pain Measurement, Protein Binding, Analgesics, Non-Narcotic, Receptor, Cannabinoid, CB1, Receptor, Cannabinoid, CB2, Rats

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