Tramadol produces outward currents by activating μ‐opioid receptors in adult rat substantia gelatinosa neurones

1 An action of a tramadol metabolite, mono‐O‐dimethyl‐tramadol (M1), on substantia gelatinosa (SG) neurones in adult rat spinal cord slices was examined by using the whole‐cell patch‐clamp technique. 2 In 41% of the neurones examined, superfusing M1 produced an outward current at −70 mV; this respon...

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Bibliographic Details
Published in:British journal of pharmacology 2005-07, Vol.145 (5), p.602-607
Main Authors: Koga, Akiko, Fujita, Tsugumi, Totoki, Tadahide, Kumamoto, Eiichi
Format: Article
Language:English
Subjects:
Analgesics, Opioid - pharmacology
Animals
antinociception
Biological and medical sciences
Enkephalin, Ala-MePhe-Gly- - pharmacology
hyperpolarization
In Vitro Techniques
Male
Medical sciences
Membrane Potentials - drug effects
Neurons - drug effects
Patch-Clamp Techniques
patch‐clamp
Pharmacology. Drug treatments
Rats
Receptors, Opioid, mu - agonists
Spinal Cord - cytology
Spinal Cord - drug effects
substantia gelatinosa
Substantia Gelatinosa - cytology
Substantia Gelatinosa - drug effects
Sympatholytics - pharmacology
Sympathomimetics - pharmacology
Tramadol
Tramadol - pharmacology
μ‐opioid receptor
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Summary:1 An action of a tramadol metabolite, mono‐O‐dimethyl‐tramadol (M1), on substantia gelatinosa (SG) neurones in adult rat spinal cord slices was examined by using the whole‐cell patch‐clamp technique. 2 In 41% of the neurones examined, superfusing M1 produced an outward current at −70 mV; this response reversed at a potential close to the equilibrium potential for K+. M1 current hardly declined and persisted for >30 min after its washout. 3 M1 current correlated in amplitude with current produced by μ‐opioid receptor agonist DAMGO in the same neurone, and largely reduced in amplitude in the presence of μ‐opioid receptor antagonist CTAP but not α2‐adrenoceptor antagonist yohimbine. In a neurone where M1 had no effect on holding currents, noradrenaline produced an outward current at −70 mV. 4 The amplitude of the M1 response, relative to that of the DAMGO response, exhibited an EC50 value of 300 μM. 5 We conclude that M1 produces a persistent hyperpolarization by activating μ‐opioid receptors in adult rat SG neurones. This could contribute to at least a part of pain alleviation produced by tramadol. British Journal of Pharmacology (2005) 145, 602–607. doi:10.1038/sj.bjp.0706225
ISSN:0007-1188
1476-5381
DOI:10.1038/sj.bjp.0706225