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At least 19 recordsLinked to original sources
PubMed1976

Effects of amitriptyline and isocarboxazid on 5-hydroxytryptophan induced head twitches in mice.

Effects of amitriptyline and isocarboxazid on brain 5-HT and 5-HIAA were examined in relation to their action on 5-HTP induced head twitches. Amitriptyline reduced 5-HTP induced head twitches but isocarboxazid increased them. Both amitriptyline and isocarboxazid caused a significant increase of brain 5-HT concentration in 5-HTP treated mice. Amitriptyline also caused a significant increase of 5-HIAA concentration, while isocarboxazid reduced 5-HIAA concentration in the brains of 5-HTP treated mice. Probenecid, which significantly increased 5-HIAA concentration without affecting brain 5-HT concentration in 5-HTP treated mice, reduced 5-HTP induced heat twitches. These results suggest that 5-HTP induced head twitches might be induced by an increase of 5-HT concentration, and reduced by an increase of 5-HIAA or a decrease of 5-HT concentration in the brains of mice.

5-Hydroxytryptophan↗
PubMed1975

The polarographic behaviour of isocarboxazid (Marplan) and its hydrolytic products.

The polarographic reduction of isocarboxazid, (Marplan) and its hydrolytic product 5-methyl-3-isoxazolylcarboxylic acid was studied both in aqueous buffered and in nonaqueous methanolic solutions. In both media, reduction occurs in the isoxazole ring resulting in a single diffusion-controlled irreversible wave corresponding to the transfer of four electrons per molecule. Addition of surfaceactive agents to the experimental solutions, did not spilt the wave into separate acts. Addition of proton donors to the methanolic solutions did, however, confirm the transfer of four protons during reduction. In acid buffer solutions the recorded polarograms furnish good means for the quantitative estimation of both compounds in the concentration range used (10(-4)-10(-3).

Chemical Phenomena↗
PubMed1975

[Effects of beta-phenylethylamine derivatives on the central nervous system. (5) The effect of intracerebral administration of tyramine on head twitching in mice pre-treated with isocarboxazid].

Effects of drugs on head-twitches induced by tyramine (Ty) in isocarboxazide (Iso) pretreated mice were studied and the following results obtained: 1) In beta-phenylethylamine derivatives, p-hydroxyamphetamine in non-treated and Iso-pretreated mice and Ty in Iso-pretreated mice produced head-twitches. 2) Injection of 5-HTP (i.c. and i.p.) into mice induced head-twitches. 3) Although head-twitches were not induced by a low dose of 5-HTP (20 mg/kg, i.p.), in Iso pretreated mice, the number of headtwitches increased markedly in the Iso-Ty treated group when Ty was injected i.c. in Iso+5-HTP (20 mg/kg) pretreated mice. 4) When Iso-Ty was injected into alpha-methyl-p-tyrosine pretreated mice, the number of head-twitches increased markedly compared with Iso-Ty treated group. 5) When Iso-Ty was injected into mice sustained with p-chlorophenylalanine, the number of head-twitches decreased markedly compared with the Iso-Ty treated group. 6) The number of head-twitches decreased markedly when Iso-Ty was injected into dimetotiazine pretreated mice, however the administration of Iso-Ty in haloperidol pretreated mice had no influence on head-twitches. 7) It is concluded that serotonin is the acting mediator in the head-twitch response.

5-Hydroxytryptophan↗
PubMed1975

[Central action of beta-phenylethylamine derivatives. (4) Effects on spontaneous motor activity and body temperature of beta phenylethyamine derivatives injected into the brain in reserpine pretreated mice].

Effects on spontaneous motor activity and body temperature of beta-phenylethlamine derivatives injected into the cerebral ventricles in reserpine or reserpine and isocarboxazide pretreated mice were investigated with the following results. 1) Each injection of tyramine (40 mug) and dopamine (40 mug) increased the spontaneous motor activity measured by the photo-cell counters method in reserpinized mice. 2) Each injection of tyramine (40 mug), dopamine (40 mug) and beta-phenylethylamine (40 mug) increased the spontaneous motor activity measured by both the wheel cage and photo-cell counters methods in reserpine and isocarboxazide-pretreated mice, but noradrenaline (20 mug) and isoproterenol (80 mug) did not increase the spontaneous motor activity as determined by both methods. 3) The injection of tyramine (40 and 80 mug), dopamine (10 and 40 mug) and p-octopamine (40 mug) increased the body temperature in reserpine and isocarboxazide pretreated mice. 4) Tyramine, dopamine and p-octopamine caused a marked increase in the body temperature as compared with control injection in reserpine and isocarboxazide-pretreated mice, whereas isoproterenol had no influence on body temperature. Our results suggest that beta-phenylethylamine derivatives have different effects in reserpinized and non-pretreated states.

Animals↗
PubMed1979

Controlled trial of trimipramine, monoamine oxidase inhibitors, and combined treatment in depressed outpatients.

A study was carried out in which 135 mildly or moderately depressed outpatients were randomly allocated to one of five groups receiving six weeks' treatment weith antidepressant drugs. The groups received a tricyclic antidepressant (trimipramine; mean dose 106 mg at night) or a monoamine oxidase inhibitor (MAOI) (phenelzine or isocarboxazid; mean doses 45 and 32 mg/day respectively), or a combination of the two (phenelzine plus trimipramine or isocarboxazid plus trimipramine). Various scales were used to measure depression before and at one, three, and six weeks of treatment, and results were assessed blindly. The tricyclic antidepressant was found to be consistently superior to the MAOIs and the combined treatments. Some differential indicators of response to the various antidepressants were found--for example, patients with initial complaints of dizziness, suicidal ideas, irritability, and insomnia and a longer duration of illness were more likely to respond to trimipramine--but these were of only modest significance. Side effects were not troublesome in any group. It is concluded that neither MAOIs nor MAOIs combined with tricyclic antidepressants are the treatment of first choice in unselected outpatients with mild or moderate depression.

Adult↗
PubMed1979

Studies on some possible biochemical treatments of primary hyperoxaluria.

The effects of some putative inhibitors of oxalate production or urinary oxalate excretion have been investigated in the Cynamolgus monkey and in patients with Type I primary hyperoxaluria (hyperoxaluria with glycollic aciduria). Sodium-1-hydroxybutan-sulphonate, D,L-phenyllactate, succinimide and isocarboxazide did not reduce the urinary oxalate excretion in the monkeys. Pyridoxine reduced the excretion of oxalate and glycollate in some patients, and its therapeutic use has been documented over a five-year period. Succinimide, which has been used by other workers for the treatment of non-hyperoxaluric stone formers, did not decrease the excretion of either oxalate or glycollate in three patients in whom it was tried. It did not change the inhibitory activity of the urine with respect to the growth and aggregation of calcium oxalate crystals in any of the three patients, and it did not have any consistent effect on the excretion of calcium oxalate crystals in the one patient who had detectable crystaluria before treatment. We have identified several metabolites of succinimide in the urine of patients taking the drug. These include 2,3-dehydrosuccinamic, 2-hydroxysuccinamic and 3-hydroxysuccinamic acids. Isocarboxazide, cholestyramine and thiamine did not affect the urinary oxalate excretion in the patients. The significance of these observations from the viewpoint of the treatment of primary hyperoxaluria is discussed.

Adolescent↗
PubMed1975

[Combination of tricyclic antidepressants and MAOI in the depressions].

This study was aimed at the assessment of therapeutic and side effects of simultaneous administration of tricyclic antidepressants and MAOI. The sample consisted of 122 patients with depressive syndromes, treated at the "Centro de Psicología Médica San Martín de Tours" (period 1970/1973), with Isocarboxazide and Trimiprimine. All patients received both drugs three times a day. The average daily dose was 20 mg of Isocarboxazide together with 125 mg of Trimiprimine. The average treatment was 70 days long. The study lead to the following conclusions: 1. There were no serious side effects. 2. The scarce side effects registered were not very different from those of the other anti-depressants. 3. The therapeutic doses were lower than those required when each drug is used alone. 4. The speed of action was higher than for each drug separately. 5. The overall percentage of improvement in patients was higher than the percentage obtained for each drug alone. 6. The lack of side effects for a theoretically risky combination of drugs is likely to be attributed to the neuroleptic action of Trimipramine.

Administration, Oral↗
PubMed1975

[Effects of beta-phenylethylamine derivatives on the central nervous system. (5) Changes in the volume of spontaneous movement in mice with intracerebral administration of tyramine].

Influence of tyramine (Ty) on behavioural changes in mice was studied and the following results obtained: 1) 30 min after Ty (160 mug, i.c.), brain noradrenaline and serotonin levels decreased while dopamine levels increased. 2) When Ty was injected i.c. into isocarboxazide (Iso) pretreated mice, spontaneous motor activity (SMA) measured by photo-cell counters method increased markedly but SMA by wheel cage method decreased. 3) When Ty was injected i.c. into Iso and p-chlorophenylalanine (p-CPA) (400 mg/kg, i.p., daily X 2) pretended mice, SMA measured by photo-cell counters method increased. While, SMA increased from 30 to 90 min after Ty, SMA measured by wheel cage method decreased till 30 min after Ty. 4) When Ty was injected i.c. into Iso and alpha-methyl-p-tyrosine (alpha-MPT) (125 mg/kg, i.p., daily X 2), SMA measured by photo-cell counters method decreased markedly when compared with Iso+saline treated group. When SMA was measured by wheel cage method, a difference between alpha-MPT+Iso-Ty treated group and Iso-saline group was not obtained. 5) When Ty was injected i.c. into p-CPA+alpha-MPT+Iso pretreated mice, SMA measured by photo-cell counters method did not show any increase compared with control group. 6) SMA produced by Iso-Ty in mice pretreated with haloperidol was significantly inhibited. A 50% dose of inhibition was seen with 0.3 mg/kg. From our results, it appears that an increase of SMA induced by Iso+Ty as revealed by the photo-cell counters method may be related to brain catecholamines and serotonin while a decrease of SMA in wheel cage method may be related to brain serotonin.

Animals↗
PubMed1977

[Central effects of beta-phenylethylamines. (8). Increase in spontaneous motor activities of mice caused by intracerebrally administered metaramino].

Metaraminol (MA) (40, 80 and 160 microng) was injected i.c. into mice and spontaneous motor activity (SMA) measured by photo-cell counters method was found to increase 30 min after the injection. Ninety min after, the SMA was restored to the saline treated control. MA (80 microng i.c.) was also injected into isocarboxazide (Iso) pretreated mice and the SMA markdly increased as compared with the Iso+saline treated group or tween+MA treated group. When MA was injected i.c. into alpha-methyl-p-tyrosine (alpha-MT) pretreated mice, the SMA significantly increased as compared with that of the alpha-MT+saline treated group, but there was a decrease as compared with that of the tween+saline or tween+MA treated group. In alpha-MT treated mice. L-Dopa restored the hyper-motor activity of animals treated with MA. Diethyldithiocarbamate (700mg/kg i.p.) had no influence, whereas haloperidol markedly blocked the hyper-motor activity induced by MA. The hyper-motor activity induced by MA in mice raised the question of a possible role of noradrenaline and dopamine in the mediation of this action.

Animals↗
PubMed1977

Effect of benzodiazepines on central serotonergic neuron systems.

Intracerebral (i.c.) injection of serotonin (5-HT) into mice induced head twitches in a dose-dependent manner at 10 min after injection. The head twitches induced by 5-HT (i.c.) were potentiated by the pretreatment of isocarboxazid (3 mg/kg i.p.), and inhibited by cyproheptadine (0.3 mg/kg i.p.), a 5-HT antagonist. Benzodiazepines such as fludiazepam and diazepam potentiated the head twitches induced by 5-HT (i.c.) in a dose-dependent manner. Mescaline (50 mg/kg i.p.) also induced head twitches in mice at 15 and 30 min after injection. Benzodiazepines potentiated the head twitches induced by mescaline in a dose-dependent manner. Cyproheptadine blocked the potentiating effect of benzodiazepines on the head twitches induced by both 5-HT (i.c.) and mescaline. By repeated administration of fludiazepam or diazepam for 5 days, the potentiating effect of both drugs on the head twitches induced by mescaline was unchanged and their anticonvulsant effects were not modified. In contrast, the potency of both drugs on muscle relaxation was significantly decreased by repeated administration. Benzodiazepines failed to change the uptake of 5-HT into the synaptosomal fractions from the rat brain. These results suggest that the pharmacological action of benzodiazepines is derived at least in part from their activating effect on 5-HT receptors.

Animals↗
PubMed1975

Activation of tryptophan pyrrolase by benzylhydrazine.

The mechanism responsible for the activation of tryptophan pyrrolase (TP) by benzylhydrazine (BZH) was investigated. The increase in holo/apo ratio of rat TP activity after addition of BZH in concentration of 1 x 10(-4)M, which is a major metabolite of isocarboxazid (ISOC), was higher than those in mice and guinea pigs. In addition, treatment with ISOC to rats (50 mg/kg i.p.) resulted in a significant increase in TP activity. These results suggested that the BZH-induced elevation of TP is at least in part due to a stimulation of conjugation step of TP activity.

Animals↗
PubMed1992

Suicide and fatal antidepressant poisoning.

OBJECTIVE: To compare the fatal toxicities of antidepressant drugs in England, Scotland and Wales 1985-1989. METHODS: Epidemiological retrospective study using Department of Health prescription data and mortality data from the Office of Population Censuses and Surveys, and the Registrar General for Scotland, for the years 1974-1989. The fatal toxicity index (FTI) of groups of drugs and individual drugs was compared with the FTI for all antidepressant drugs for the years 1985-1989. RESULTS: Of 3,604 single antidepressant deaths between 1975 and 1989, the majority (70.95%) were from amitriptyline or dothiepin. The mean FTI for all drugs for the years 1985-1989 was 35.6; the FTIs for dothiepin, amitriptyline, nortriptyline and tranylcypromine were significantly higher than the mean of all, while those for clomipramine, lofepramine, fluvoxamine, trimipramine, maprotiline, trazodone, mianserin, protriptyline, isocarboxazid and phenelzine were lower. The FTI for the older tricyclic drugs was higher at 43.03 (p < 0.001). The FTI for the monoamine oxidase inhibitors, of 27.03 (p = 0.045), and for all drugs introduced after 1973, of 5.32 (p < 0.001), were each significantly lower than the mean of all drugs. CONCLUSIONS: Overdose deaths from antidepressants have not decreased over the last 15 years. A trend away from prescribing drugs with a higher fatal toxicity index in favour of those with a lower index, would reduce the number of deaths from antidepressant poisoning.

Acute Disease↗
PubMed1978

Sensitization to the generalized Shwartzman reaction by catechol-O-methyltransferase inhibitors.

The generalized Shwartzman reaction (GSR) was produced by a single injection of endotoxin in male rats pretreated with catechol-o-methyltransferase (COMT) inhibitors (tropolone, pyrogallol). Such a result was not obtained with inhibitors (pargyline, phenelzine, isocarboxazide) of the monoamine oxidase (MAO). The inhibitors of the COMT were found to enhance the action of endotoxin on the coagulation system such as evidenced by the increased consumptions of Hageman factor, fibrinogen, and platelets. Tropolone-treated rabbits did not require exogenous stimulation of alpha-adrenergic receptor sites by norepinephrine to localize thrombi in the glomerular capillaries when Hageman factor was activated by ellagic acid and fibrinolysis inhibited by epsilon-amino-caproic acid. It is concluded that interference with the degradation of circulating catecholamines results in sensitization to the generalized Shwartzman reaction.

Animals↗
PubMed1976

Combining tricyclic and monoamine oxidase inhibitor antidepressants.

The charts of 150 inpatients and 51 outpatients treated with a monoamine oxidase inhibitor (MAOI)-tricyclic antidepressant combination were reviewed. The incidence and severity of side effects among the patients on the combined regimen were essentially the same as those seen in the control groups. There were no deaths or strokes resulting from use of this regimen. The most frequent troublesome side effect was orthostatic hypotension. We conclude that the use of a MAOI-tricyclic combination in oral therapeutic doses is safe. However, the efficacy of this combination has not yet been proved, and it may be particularly toxic if taken in an overdose.

Amitriptyline↗