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Biomedical subjects

B Hamberger

Publications and source records attributed to B Hamberger.

At least 127 records · Page 7Linked to original sources
PubMed1975

Effect of ergot drugs on central 5-hydroxytryptamine neurons: evidence for 5-hydroxytryptamine release or 5-hydroxytryptamine receptor stimulation.

In combined biochemical and functional studies it has been possible to show that ergocornine (0.5-5 mg/kg) and the ergolene derivative (5R,8R)-8-(4-p-methoxyphenyl-1-piperazinylmethyl)-6-methylergolene (PTR 17402; MPME) (0.25-5 mg/kg) reduce in a dose-dependent way brain 5-hydroxytryptamine (5-HT) turnover in rat as evaluated with the tryptophan hydroxylase inhibitor, alpha-propyl-dopacetamide (H 22/54), whereas 2-Br-alpha-ergocryptine (CB 154; Br-EC) had no effect on brain 5-HT turnover. Effects on 5-HT receptor activity were evaluated using the extensor hindlimb reflex of acutely spinalized rats. It was found that ergocornine increased the 5-HT receptor activity independent of presynaptic 5-HT stores and that it didnot have any effects on uptake, retention and spontaneous overflow of 3-H-5-HT in vitro but reduced the fiedl stimulation-induced release of 3-H-5-HT in vitro. Therefore, it is suggested that ergocornine is a 5-HT recpetor-stimulating agent, an effect which may lead to reduction of nervous impulse flow in the 5-HT neurons and subsequently of 5-HT release and turnover. MPME, on the other hand, seems to increase 5-HT receptor release of 5-HT stores, mainly from extragranular sites. Thus, the increase in extensor reflex activity found after MPME was reduced by reserpine and H 22/54 and enhanced by nialamide and in vitro MPME markedly increased 3-H-5-HT overflow in cortical slices of nialamide-pretreated rats and inhibited uptake and retention of 3-H-5-HT (EC50 equals 1.6 times 10-minus 6 M) in cortical slices of normal rats. Inhibition of the 5-HT membrane pump does not seem to be of any major importance, since chlorimipramine was only weakly active on the extensor reflex in the pharmacological models used and since MPME did not block but rather enhanced the 5-HT depletion caused by 4-methyl-alpha-ethyl-m-tyramine. It is suggested that MPME is a releaser of extragranular 5-HT stores leading to increased 5-HT receptor activity and reduction of 5-HT turnover in the same way as indicated for ergocornine. This new ergolene derivative may represent a new class of antidepressant drugs acting via release of extragranular 5-HT stores.

Animals↗
PubMed1971

Drug-induced changes in the release of ( 3 H)-noradrenaline from field stimulated rat iris.

1. Isolated rat irides were incubated with [(3)H]-noradrenaline [(3)H-NA] (10(-7)M), superfused with buffer and then stimulated by an electrical field. The effect of desipramine, clonidine, phentolamine, phenoxybenzamine, GD131, normetanephrine and 4-tropolone-acetamide on the stimulation-induced overflow of [(3)H]-NA was tested by adding the drug to the superfusing buffer. The effect of pretreatment with phentolamine or phenoxybenzamine on the stimulation-induced overflow of [(3)H]-NA was also studied.2. The effect of desipramine, clonidine, phentolamine, phenoxybenzamine and GD131 on uptake of [(3)H]-NA in isolated irides was determined.3. Desipramine moderately increased the stimulation-induced overflow at concentrations which almost completely inhibited neuronal uptake. It was calculated that in the isolated rat iris 30-40% of the released [(3)H]-NA is inactivated by reuptake into the nerve terminal. This figure may represent the true reuptake percentage in this preparation. Desipramine-induced inhibition of [(3)H]-NA release from the nerve terminal, possibly via a negative feed-back mechanism, may also contribute to this low figure.4. Phentolamine and phenoxybenzamine, in concentrations or doses which did not inhibit neuronal uptake of [(3)H]-NA, consistently increased the stimulation-induced overflow. This increase was further augmented when neuronal uptake was inhibited.5. The alpha-adrenoceptor stimulating drug clonidine decreased the stimulation-induced overflow.6. GD131, normetanephrine and 4-tropolone-acetamide did not greatly affect the stimulation-induced overflow of [(3)H-NA].7. It is concluded that the increased [(3)H]-NA overflow obtained after alpha-adrenoceptor blockade is due to an increased [(3)H]-NA release from the nerve terminals.

Acetamides↗