Fluorometric estimation of meteraminol and related compounds

123

I The effects of mianserin and of selected tricyclic antidepressants were compared in a number of monoamine uptake models. 2 The ability of mianserin to block the noradrenergic neurone membrane amine pump of rabbit brain stem slices was comparable to that of imipramine and amitriptyline and less than that of desipramine and nortriptyline. Both mianserin and desipramine were competitive inhibitors of noradrenaline uptake in vitro. The effect of mianserin on noradrenaline uptake in vivo was studied both peripherally and centrally. The ability of 6-hydroxydopamine to lower rat heart noradrenaline levels was found to be very sensitive to inhibition by tricyclic antidepressants. Mianserin was active in this model. However, its ability to block the 6-hydroxydopamine-induced fall in rat heart noradrenaline concentration was appreciably less than that of the tricyclics studied. 3 Mianserin, like tricyclic antidepressants, was essentially devoid of effect on dopamine uptake both in vitro and in vivo. 4 The ability of mianserin to inhibit [3H]-5-hydroxytryptamine uptake by rat hypothalamic synaptosomes was appreciably less than that of the tricyclic antidepressants studied. Mianserin was essentially devoid of effect on rat brain 5-hydroxytryptamine uptake in vivo.

“…After weighing, tissues were homogenized in 0.4 N perchloric acid. The fluorometric procedure of Shore & Alpers (1964) was used to analyse the slice content of (-)MA.…”

Section: Methodsmentioning

confidence: 99%

EFFECTS OF MIANSERIN, A NEW ANTIDEPRESSANT, ON THE in vitro AND in vivo UPTAKE OF MONOAMINES

Goodlet¹,

Mireylees²,

Sugrue³

1977

123

“…Striata from two rats were pooled and striatal a-methyl-mtyramine (MMTA) concentrations measured (Shore & Alpers, 1964 …”

Section: Methodsmentioning

confidence: 99%

The Effects of Acutely Administered Analgesics on the Turnover of Noradrenaline and Dopamine in Various Regions of the Rat Brain

Sugrue¹

1974

1 Noradrenaline and dopamine turnover rates were determined following blockade of synthesis by a-methyl-p-tyrosine. Morphine, pentazocine and methadone had no effect on steady state levels or on turnover of noradrenaline in whole brain and in the hypothalamus. Although morphine was without action on medulla-pons noradrenaline steady state levels, a drug-induced increase in turnover rate was observed which was antagonized by pretreatment with naloxone (5 mg/kg). Pentazocine and methadone failed to alter either the steady state level of noradrenaline in the medulla-pons or its turnover rate. 2 Morphine accelerated the decline in striatal a-methyl-m-tyramine levels following subcutaneous injection of a-methyl-m-tyrosine 18 h previously. 3 All three drugs increased the turnover of dopamine in whole brain and corpus striatum although the striatal effect was prevented by naloxone pretreatment. The minimum doses of morphine, pentazocine and methadone required to elicit a significant effect on striatal dopamine turnover were 10 mg/kg, 30 mg/kg and 10 mg/kg respectively. 4 The possibility of a dopaminergic involvement in the antinociceptive effect of analgesics is discussed.

“…In this procedure 101-9+2-1% (12 estimations) of added metaraminol was recovered. In some of the experiments, metaraminol was extracted by the butanol-heptane procedure of Shore & Alpers (1964); the mean recovery of added metaraminol was 52-5 ±+32% (6 estimations). In all experiments in which the effect of drugs on the uptake of metaraminol was studied the ZnSO4-procedure was used.…”

Section: Incubation Of Plateletsmentioning

confidence: 99%

“…The metaraminol content of platelets was determined after precipitating the proteins as described above. The metaraminol content of the supernatant was measured by the o-phtaldialdehyde method of Shore & Alpers (1964). In this procedure 101-9+2-1% (12 estimations) of added metaraminol was recovered.…”

Section: Incubation Of Plateletsmentioning

confidence: 99%

The effect of narcotic analgesics on the uptake of 5‐hydroxytryptamine and (—)‐metaraminol by blood platelets

Ahtee

Saarnivaara

1973

Summary1. The effects of narcotic analgesic and related drugs were studied on the uptake of 5-hydroxytryptamine (5-HT) and (-)-metaraminol by blood platelets.2. The most potent drug in inhibiting the uptake of 5-HT (10 FLM) by human platelets was methadone, followed by pentazocine>piminodine-pethidineanileridine cyclazocine thebaine > dextropropoxyphene. Alphaprodine, papaverine, apomorphine, nalorphine, codeine, and morphine were almost without effect. Methadone was slightly less active than desipramine, and had 10% of the activity of imipramine under similar conditions. Naloxone did not antagonize the effect of methadone on 5-HT uptake.3. The most potent inhibitor of metaraminol (3 jM) uptake by human platelets was piminodine, followed by pentazocineRanileridine>cyclazocine= methadone > dextropropoxyphene -thebaine > papaverine -alphaprodine >pethidine>morphine. The activity of morphine was 1% of that of piminodine. Piminodine was more potent than desipramine and protriptyline under similar conditions. The order of potency of drugs studied in inhibiting the uptake of metaraminol by rabbit platelets was similar to that obtained with human platelets. 4. The effects of the analgesics studied on inhibiting uptake of monoamines did not correlate with their pain-relieving properties. IntroductionThe uptake and storage of 5-hydroxytryptamine (5-HT) by blood platelets closely resembles that which occurs in neurones. Moreover, the inhibition of this uptake by drugs is similar to that found in neurones (Paasonen, 1968;Paasonen, Ahtee & Solatunturi, 1971;Stacey, 1961; Todrick & Tait, 1969). We have recently shown that the orders of potency of tricyclic anti-depressants in inhibiting the uptake of 5-HT and a noradrenaline analogue, metaraminol, by human blood platelets were different. These drugs had a similar order of activity in inhibiting the uptake of 5-HT by platelets and in preventing the uptake of 5-HT by neurones, whereas their effects on the uptake of metaraminol by platelets paralleled their potencies in blocking the uptake of noradrenaline into neurones (Ahtee & Saarnivaara, 1971b).The present work was undertaken to find out if narcotic analgesics inhibit the uptake of 5-HT and metaraminol by platelets because there is evidence that several