Brain Tryptophan Perturbation in Hepatic Encephalopathy: Implications for Effects by Neuropsychoactive Drugs in Clinical Practice

Altered open-field behavior in experimental chronic hepatic encephalopathy after single venlafaxine and citalopram challenges

“…For the SSRIs this statement is, to the best of our knowledge, based on a single open-labeled study of ßuvoxamine in which no overt worsening of the HE was seen after a 2-week observation period without any pharnacokinetic control (Holm et al 1988). Moreover, studying only pharmacokinetic parameters is clearly inadequate for predicting possible CNS e¤ects in patients with liver insu¦ciency (as suggested by the results obtained in the present study, see also Wikell et al 1998 and overview by Bengtsson et al 1997).…”

“…Disturbances in CNS monoaminergic systems and 5-HT innervated systems in particular, have received much attention in HE research (Bengtsson 1987(Bengtsson , 1992Bengtsson et al 1997). Several investigations have shown markedly increased CNS metabolism of 5-HT in the PCS rat (Bengtsson et al 1985(Bengtsson et al , 1986(Bengtsson et al , 1988Mans and Hawkins 1986;Bergeron et al 1990).…”

“…The PCS rat displays several neurochemical, neurophysiological and neurohistopathological changes resembling those seen in human chronic HE, including substantially increased blood and brain ammonia and tryptophan levels and enhanced brain serotonin (5-hydroxytryptamine; 5-HT) metabolism (for recent overviews see, e.g. Mousseau and Butterworth 1994;Bengtsson et al 1997). The most frequently reported behavioral change in PCS rats has been that of hypoactivity, especially evidenced as lowered spontaneous locomotor activity (Tricklebank et al 1978(Tricklebank et al , 1981Martin et al 1980Martin et al , 1986Bengtsson et al 1986Bengtsson et al , 1988Bengtsson 1987;Ribeiro et al 1992;Apelqvist et al 1997Apelqvist et al , 1998.…”

“…Furthermore, these patients may have altered diurnal rhythms, particularly with respect to sleep pattern (Adams and Foley 1953;Elsass et al 1978;Conn and Lieberthal 1979;Jones and Gammal 1988). Such diverse symptomatology may indicate multilevel neuronal dysfunction, possibly reßecting primary neurotransmission alteration in the brain (Mousseau and Butterworth 1994;Bengtsson et al 1997).…”

Plasma and Brain Levels of Oxindole in Experimental Chronic Hepatic Encephalopathy: Effects of Systemic Ammonium Acetate and L‐Tryptophan

“…Furthermore, a profound increase in the brain metabolism of the L-tryptophan-derived neurotransmitter serotonin has been demonstrated as prevalent in experimental hepatic encephalopathy in vivo Bengtsson et al 1997). Much research has been focused on the possible significance of the disturbed L-tryptophan/ serotonin metabolism in the pathogenesis of chronic hepatic encephalopathy, but to date no general consensus has been reached regarding this issue .…”