The Journal of pharmacology and experimental therapeutics
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J. Pharmacol. Exp. Ther. · May 2001
Differential effect of gabapentin on neuronal and muscle calcium currents.
Calcium channels modulate cell function by controlling Ca(2+) influx. A main component of these proteins is the alpha 2/delta subunit. Nevertheless, how this subunit regulates channel activity in situ is unclear. ⋯ Muscle cells showed a more variable expression of alpha 2/delta subunits than did DRG cells. Our results suggest a possible participation of the alpha 2/delta subunit in the action of GBP. Our data also indicate that GBP inhibits Ca(2+) channels in a use- and voltage-dependent manner at a therapeutically relevant concentration.
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J. Pharmacol. Exp. Ther. · May 2001
In vivo pharmacological characterization of SoRI 9409, a nonpeptidic opioid mu-agonist/delta-antagonist that produces limited antinociceptive tolerance and attenuates morphine physical dependence.
Repeated exposure to mu-opioid analgesics produces unwanted side effects, including tolerance and physical dependence. delta-Opioid antagonists attenuate development of morphine tolerance and physical dependence. We recently reported that SoRI 9409, a mixed mu-agonist/delta-antagonist, produces antinociception with limited development of tolerance after repeated i.c.v. injections. The current studies report on a more complete characterization of the compound in male ICR mice. ⋯ SoRI 9409 (10 mg/kg i.p.) elicited much less vertical jumping than naloxone (10 mg/kg i.p.) in acute and chronic morphine dependence models. SoRI 9409 also suppressed withdrawal jumping when coadministered with naloxone. These studies indicate that SoRI 9409 acts primarily as a partial mu-agonist/delta-antagonist and supports the hypothesis that this type of compound may have a better therapeutic profile than currently available mu-agonists.