Neural response to lidocaine in healthy subjects.
Recent studies suggest that some of cocaine's central nervous system (CNS) effects may be mediated through its sodium channel inhibiting local anesthetic properties. Local anesthetics that lack cocaine's strong affinity for the dopamine transporter (DAT) also produce sensory and mood effects, further suggesting a role for this neural pathway. Due to an absence of affinity at the DAT, the local anesthetic lidocaine may offer the potential to assess sodium channel activity in vivo in humans. To assess the utility of lidocaine as a CNS probe, we determined regional cerebral blood flow (rCBF) with single photon emission computed tomography (SPECT) following the intravenous administration of lidocaine (0.5 mg/kg) and compared this response to procaine (0.5 mg/kg and 1.0 mg/kg), a local anesthetic with partial affinity for the DAT, and saline. Infusions were administered in nine healthy female controls over a 10-day period with at least 2 days between each scan. Increased rCBF was observed following lidocaine, relative to saline, in the insula, caudate, thalamus, and posterior cingulate. Decreased rCBF was detected in a different region of the posterior cingulate. In general, increases in rCBF were more marked following lidocaine relative to procaine. Mood and sensory changes following lidocaine were limited and significantly less than those induced by either dose of procaine. There were no significant changes in blood pressure or heart rate following either medication. These findings suggest that lidocaine can be safely used to assess sodium channel function in persons with addictive and other psychiatric disorders.
Adinoff
Bryon
B
Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, United States. bryon.adinoff@utsouthwestern.edu
Devous
Michael D
MD
Cooper
Donald C
DC
Best
Susan E
SE
Harris
Thomas S
TS
Williams
Mark J
MJ
D000328:Adult; D000339:Affect / Q000187:drug effects; D000779:Anesthetics, Local / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000098:blood supply* / Q000000981:diagnostic imaging / Q000187:drug effects*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008012:Lidocaine / Q000008:administration & dosage / Q000494:pharmacology*; D008875:Middle Aged; D011343:Procaine / Q000008:administration & dosage / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects; D015899:Tomography, Emission-Computed, Single-Photon
D000779:Anesthetics, Local; D050483:Dopamine Plasma Membrane Transport Proteins; D011343:Procaine; D008012:Lidocaine