Continuous Nicotine Monitors for Personal Nicotine Pharmacokinetics: A Receptor-Aware Research Agenda
Abstract
A minimally invasive "continuous nicotine monitor" (CNM) would resolve the dynamic nicotine concentration, [nicotine]t, faced by high-sensitivity nicotinic acetylcholine receptors (nAChRs) during and after nicotine intake by individual subjects. Motivations: "Know the potential enemy at an individual level". Smoking or vaping produces an initial "bolus" of nicotine in the blood and brain, lasting ~5 min with a peak concentration of ~ 100-200 nM. The bolus largely governs reinforcement, reward, and cognitive enhancement. A prolonged declining phase of [nicotine], with a half-time of 1 to 4 h, largely suppresses withdrawal symptoms and governs the known cell biology of addiction. Next, "Know the potential therapy", because individual [nicotine]t records will be useful during research on the effectiveness of nicotine replacement therapy. Finally, "Know the physiology". The only three known effects on nAChRs in cerebrospinal fluid (CSF) at the relevant [nicotine]t are activation, desensitization, and chaperoning/upregulation. Therefore, additional mechanistic insights will arise from correlating [nicotine]t with readily measurable physiological data on those effects in molecular, cellular, and brain slice systems and animal models. Interstitial fluid is the appropriate compartment for a CNM. The molecular sensor technology could employ fluorescence, as shown by progress on measuring [nicotine]t with improved variants of intensity-based nicotine-sensing fluorescent reporters…
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