Rainer Knörle

Pharmacological studies in an herbal drug combination of St. John's Wort (Hypericum perforatum) and passion flower (Passiflora incarnata): in vitro and in vivo evidence of synergy between Hypericum and Passiflora in antidepressant pharmacological models.

Extracts of Hypericum, Passiflora and Valeriana are used for the treatment of mild depression and anxiety. We were interested whether a combination of Hypericum and Passiflora exerts comparable effects to Hypericum alone. We used two well-established models for investigating extracts for their anti-depressant activity, namely the effects on synaptic uptake of serotonin and the forced-swimming-test. We show here for the first time, that Passiflora significantly enhances the pharmacological potency of Hypericum in both models. Our data suggest that anti-depressive therapeutic effects of Hypericum are possible with lower doses, when it is combined with Passiflora, than with mono-preparations of Hypericum.

Drug accumulation in melanin: an affinity chromatographic study.

The affinity of several drugs to melanin has been indirectly assessed using an affinity chromatographic approach based on immobilized melanin. Plots of the retention of the drugs on the affinity column versus the number of molecules applied were fitted best by nonlinear, exponential curves characteristic for each drug. These curves reflect the complexity of the binding behaviour, consisting of a variety of hydrogen bonding, hydrophobic or ionic interactions as well as cooperative or anti-cooperative interactions between the drug molecules and melanin. The nonlinear fitting procedure was based on a descriptive function and allowed to discriminate the binding behaviour according to parameter estimates which specified the investigated drugs.

Strychnine-sensitive glycine receptors inducing [3H]-acetylcholine release in rat caudatoputamen: a new site of action of ethanol?

Abstract In the present study acute effects of ethanol on [3H]-acetylcholine ([3H]-ACh) release induced by activation of strychnine-sensitive glycine receptors in superfused slices of rat caudatoputamen were investigated. The glycine-evoked [3H]-ACh release (lg EC50 = –4.10, CI95 = [–4.14, –4.05]) was inhibited by strychnine in a competitive manner (pA2 = 6.86, CI95 = [6.61, 7.08]). Release of [3H]-ACh could also be induced by L-serine. L-serine was less potent than glycine (lg EC50 = –2.61, CI95 = [–2.69, –2.52]). Both glycine and L-serine showed similar maximum effects (Emax(glycine) = 1.34, CI95 = [1.24, 1.45]; Emax(L-serine) = 1.19, CI95 = [1.09, 1.32]). Ethanol at concentrations of 2‰ (= 34 mM) and 4‰ (= 68 mM) inhibited glycine-evoked [3H]-ACh release in a manner like the competitive antagonist strychnine, however with lower potency. The pA2 of ethanol was 1.19, CI95 = [0.85, 1.41], at 2‰ [v/v] and 1.51, CI95 = [1.19, 1.78] at 4‰ ethanol. Similar to its action on glycine-evoked [3H]-ACh release, ethanol at 4‰ [v/v] also inhibited L-serine-evoked transmitter release in a competitive-like fashion (pA2 = 0.83, CI95 = [–0.15, 1.18]). We conclude, that strychnine-sensitive glycine receptors, mediating [3H]-ACh release in the rat caudatoputamen, might represent a new site of action of ethanol.

Aspartate, glutamate, glutamine, glycine and γ-aminobutyric acid in human bioptic neocortical areas: comparison to autoptic tissue

Amino acid concentrations were determined by high performance liquid chromatography in distinct areas of human neocortex of autoptic and bioptic origin. The concentrations in autoptic tissue were similar in all cortical areas which may be explained by postmortem proteolysis, abolishing regional differences seen in bioptic tissue. Aspartate, glutamate, glycine and gamma-aminobutyric acid concentrations were lower, but glutamine levels were higher, in biopsied than in autopsied tissue. Glycine and gamma-aminobutyric acid concentrations increased with the age of biopsied patients. The differences seen suggest that only amino acid concentrations determined in bioptic tissue may yield a reliable data base for the interpretation of pathological alterations in neocortical biopsies of patients with brain diseases.