β‐Carbolines in chronic alcoholics following trauma

Abstract

In our society every second polytraumatized patient is a chronic alcoholic. A patient's alcohol-related history is often unavailable and laboratory markers are not sensitive or specific enough to detect alcohol-dependent patients who are at risk of developing alcohol withdrawal syndrome (AWS) during their post-traumatic intensive care unit (ICU) stay. Previously, it has been found that plasma levels of norharman are elevated in chronic alcoholics. We investigated whether beta-carbolines, i.e. harman and norharman levels, could identify chronic alcoholics following trauma and whether possible changes during ICU stay could serve as a predictor of deterioration of clinical status. Sixty polytraumatized patients were transferred to the ICU following admission to the emergency room and subsequent surgery. Chronic alcoholics were included only if they met the DSM-III-R and ICD-10 criteria for alcohol dependence or chronic alcohol abuse/harmful use and their daily ethanol intake was > or =60 g. Harman and norharman levels were assayed on admission and on days 2, 4, 7 and 14 in the ICU. Harman and norharman levels were determined by high pressure liquid chromatography. Elevated norharman levels were found in chronic alcoholics (n = 35) on admission to the hospital and remained significantly elevated during their ICU stay. The area under the curves (AUC) showed that norharman was comparable to carbohydrate-deficient transferrin (CDT) and superior to conventional laboratory markers in detecting chronic alcoholics. Seventeen chronic alcoholics developed AWS; 16 of these patients experienced hallucinations or delirium. Norharman levels were significantly increased on days 2 and 4 in the ICU in patients who developed AWS compared with those who did not. An increase in norharman levels preceded hallucinations or delirium with a median period of approximately 3 days. The findings that elevated norharman levels are found in chronic alcoholics, that the AUC was in the range of CDT on admission and that norharman levels remained elevated during the ICU stay, support the view that norharman is a specific marker for alcoholism in traumatized patients. Since norharman levels increased prior to the onset of hallucinations and delirium it seems reasonable to investigate further the potential role of norharman as a possible substance which triggers AWS.

Contribution of monoamine oxidase (MAO) inhibition to tobacco and alcohol addiction

“…Following smoking of a cigarette, norharman serum levels increased from 20 pg/ml to 70-560 pg/ml (Breyer-Pfaff et al, 1996). After one cigarette, the median plasma levels of norharman (0.87 nM; 116 pg/ml) are high enough (Rommelspacher et al, 2002;Spies et al, 1996) to inhibit MAO in vivo by some 50%, though the duration of their effects is relatively short due to the short elimination half-life (t 1/2 of approximately 1 h) (Rommelspacher et al, 2002). In contrast to norharman, the beta-carboline harman is no potent inhibitor of MAO-B, but effectively inhibits MAO-A, with reported K i values of 55 nM (Herraiz and Chaparro, 2005) and 220 nM (Rommelspacher et al, 2002).…”

Agmatine Inhibits Behavioral Sensitization to Ethanol Through Imidazoline Receptors

“…It is a considered endogenous ligand for imidazoline receptors (De Vos et al., ; Raasch et al., , ; Reis and Regunathan, ). In addition, several reports have demonstrated the effect of imidazoline receptor ligands on EtOH actions, intake, and development of dependence or of withdrawal syndrome (Dobrydnjov et al., ; Lewis et al., ; Mao and Abdel‐Rahman, ; Rommelspacher et al., ; Spies et al., ; Taksande et al., ; Uzbay et al., ). In light of available reports, it is expected that agmatine might influence sensitization to behavioral effects of EtOH.…”