Neural response to lidocaine in healthy subjects

Abstract

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 ten-day period with at least two days between each scan. Increased rCBF was observed following lidocaine, relative to saline, in the insula, caudate, thalamus, 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.

Langanhaltende Besserung von somatischen und psychovegetativen Störungen unter Procain-Infusionen: Eine multizentrische Anwendungsbeobachtung

“…Nach der Penetration durch die Bluthirnschranke erhöht Procain die Durchblutung, und damit die neuronale Aktivität, in verschiedenen zentralnervösen Kerngebieten wie dem präfrontalen Kortex, den Basalganglien und dem limbischen System [7,8,9]. Nachgewiesen sind unter anderem auch die Hemmung des DAT und die Zunahme der Verfügbarkeit von Dopamin im synaptischen Spalt [5,6] sowie die Hemmung der Serotonin- und Noradrenalin-Wiederaufnahme in vitro [19].…”

“…Im Tierversuch, einschließlich Primaten, wurde die Bindung von Procain unter anderem an muskarinerge Acetylcholin-Rezeptoren sowie an den Dopamin-Wiederaufnahmetransporter (DAT) nachgewiesen [4,5,6]. Am Menschen verursacht die intravenöse Gabe von Procain Änderungen der zerebralen Durchblutung, etwa im Kortex und im limbischen System, und verändert die Stimmungslage [7,8,9]; manche dieser Procain-Wirkungen ähneln denen von Cocain, allerdings in einem schwächeren Ausmaß. …”

The Procaine-Base-Infusion: a Review after twenty Years of Use

“…In 2016, SABIT et al, showing that the use of procaine combined with carboplatin was the most effective treatment for diminishing the global level of DNA methylation in colon cancer cells [31]. Well examined is also the central modulation of Procaine acting on the stress axis of limbic system with anti-depressive and psycho-analeptic action [32][33][34][35][36].…”

“…80 % of patients) it is advised especially in chronic diseases, to continue with a longterm therapy using the helpful dosage for longer intervals, e.g. one till twice a month [34][35][36].…”

“…As expected, in approximately 6% of patients a short-time reduction in bloodpressure and vasovagal syncope situations can occur during the application. All these symptoms disappear within few minutes, especially after reducing the infusion speed [34,63].…”