{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T04:43:18Z","timestamp":1791088998136,"version":"4.1.0"},"reference-count":49,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Pharmacol"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                        <jats:title>Background<\/jats:title>\n                        <jats:p>Gabapentin and pregabalin have wide-ranging therapeutic actions, and are structurally related to the inhibitory neurotransmitter GABA. Gabapentin, pregablin and GABA can all modulate voltage-activated Ca<jats:sup>2+<\/jats:sup> channels. In this study we have used whole cell patch clamp recording and fura-2 Ca<jats:sup>2+<\/jats:sup> imaging to characterise the actions of pregabalin on the electrophysiological properties of cultured dorsal root ganglion (DRG) neurones from neonatal rats. The aims of this study were to determine whether pregabalin and gabapentin had additive inhibitory effects on high voltage-activated Ca<jats:sup>2+<\/jats:sup> channels, evaluate whether the actions of pregabalin were dependent on GABA receptors and characterise the actions of pregabalin on voltage-activated potassium currents.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Results<\/jats:title>\n                        <jats:p>Pregabalin (25 nM \u2013 2.5 \u03bcM) inhibited 20\u201330% of the high voltage-activated Ca<jats:sup>2+<\/jats:sup> current in cultured DRG neurones. The residual Ca<jats:sup>2+<\/jats:sup> current recorded in the presence of pregabalin was sensitive to the L-type Ca<jats:sup>2+<\/jats:sup> channel modulator, Bay K8644. Saturating concentrations of gabapentin failed to have additive effects when applied with pregabalin, indicating that these two compounds act on the same type(s) of voltage-activated Ca<jats:sup>2+<\/jats:sup> channels but the majority of Ca<jats:sup>2+<\/jats:sup> current was resistant to both drugs. The continual application of GABA, the GABA<jats:sub>B<\/jats:sub> receptor antagonist CGP52432, or intracellular photorelease of GTP-\u03b3-S had no effect on pregabalin-induced inhibition of Ca<jats:sup>2+<\/jats:sup> currents. Although clear inhibition of Ca<jats:sup>2+<\/jats:sup> influx was produced by pregabalin in a population of small neurones, a significant population of larger neurones showed enhanced Ca<jats:sup>2+<\/jats:sup> influx in response to pregabalin. The enhanced Ca<jats:sup>2+<\/jats:sup> influx evoked by pregabalin was mimicked by partial block of K<jats:sup>+<\/jats:sup> conductances with tetraethylammonium.<\/jats:p>\n                        <jats:p>Pregabalin produced biphasic effects on voltage-activated K<jats:sup>+<\/jats:sup> currents, the inhibitory effect of pregabalin was prevented with apamin. The delayed enhancement of K<jats:sup>+<\/jats:sup> currents was attenuated by pertussis toxin and by intracellular application of a (Rp)-analogue of cAMP.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Conclusions<\/jats:title>\n                        <jats:p>Pregabalin reduces excitatory properties of cultured DRG neurones by modulating voltage-activated Ca<jats:sup>2+<\/jats:sup> and K<jats:sup>+<\/jats:sup> channels. The pharmacological activity of pregabalin is similar but not identical to that of gabapentin. The actions of pregabalin may involve both extracellular and intracellular drug target sites and modulation of a variety of neuronal conductances, by direct interactions, and through intracellular signalling involving protein kinase A.<\/jats:p>\n                     <\/jats:sec>","DOI":"10.1186\/1471-2210-4-14","type":"journal-article","created":{"date-parts":[[2004,8,10]],"date-time":"2004-08-10T06:35:20Z","timestamp":1092119720000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":71,"title":["A study comparing the actions of gabapentin and pregabalin on the electrophysiological properties of cultured DRG neurones from neonatal rats"],"prefix":"10.1186","volume":"4","author":[{"given":"David","family":"McClelland","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhian M","family":"Evans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Barkworth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duncan J","family":"Martin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roderick H","family":"Scott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2004,8,4]]},"reference":[{"key":"64_CR1","doi-asserted-by":"publisher","first-page":"199","DOI":"10.2174\/1570159033477062","volume":"1","author":"M-M Backonja","year":"2003","unstructured":"Backonja M-M: Symptomatic treatment of chronic neuropathic pain with gabapentin clinical practice and research perspective. 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