Trifluoperazine modulates [3H]resiniferatoxin binding by human and rat vanilloid (capsaicin) receptors and affects 45Ca uptake by adult rat dorsal root ganglion neurones

G. Acs, M. Palkovits, P. M. Blumberg

Research output: Contribution to journalArticle

22 Citations (Scopus)


Optimum treatment of neuropathic pain includes the use of adjuvant analgesics such as antipsychotic drugs and tricyclic antidepressants. Although the mechanism of their analgesic action is not known, it is possible that such agents act directly on pain pathways. The ability of capsaicin and its analogs to selectively deactivate primary afferent neurons provides a basis for their use in human therapy to relieve a number of chronic pain conditions. We examined whether the phenothiazine antipsychotic drug trifluoperazine (TFP) as well as other neuroleptics and tricyclic antidepressants have an effect on the agonist binding properties and the activation of the human and rat vanilloid receptors. Binding of [3H]resiniferatoxin (RTX) to membrane preparations of human dorsal horn and rat whole spinal cord was affected by TFP in a biphasic fashion, with an initial 25 and 65% enhancement of [3H]RTX binding, respectively, preceding inhibition. The apparent K(i) values for inhibition were 3.93 ± 0.13 μM for human dorsal horn and 7.91 ± 0.62 μM for rat spinal cord. Scatchard analyses revealed that TFP affected both the affinity and the cooperativity of [3H]RTX binding by the receptors, leaving the receptor density unaltered. Similar effects on [3H]RTX binding to rat spinal cord membranes were also induced by other antipsychotic phenothiazines and other types of antipsychotics, by phenothiazines without antipsychotic actions, as well as by tricyclic antidepressants. In cultures of dorsal root ganglion neurones, TFP at concentrations that increased [3H]RTX binding (1-3 μM) also induced an increase in 45Ca uptake; this increase was absent in cultures prepared from capsaicin desensitized animals. Furthermore, TFP at a concentration of 10 μM also increased the extent of 45Ca uptake induced by 0.3 μM capsaicin. Our results suggest that at therapeutic concentrations (0.5-5.0 μM) TFP may increase the affinity of the vanilloid receptor for agonists and thereby accelerate its desensitization.

Original languageEnglish
Pages (from-to)1090-1098
Number of pages9
JournalJournal of Pharmacology and Experimental Therapeutics
Issue number3
Publication statusPublished - Jan 1 1995

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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