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Biomedical subjects

I M McIntyre

Publications and source records attributed to I M McIntyre.

At least 19 recordsLinked to original sources
PubMed1994

Chronic effect of the irreversible and reversible selective MAO-A inhibitors on rat pineal melatonin biosynthesis.

Acute administration of the irreversible MAO-A inhibitor, clorgyline (2.0 mg/kg, s.c.) and the reversible MAO-A inhibitor, moclobemide (10 mg/kg, s.c.), increased rat pineal melatonin and related indoles content (HPLC-fluorimetric method). Chronic (21 days) administration of clorgyline attenuated the acute effect of clorgyline on pineal melatonin biosynthesis. The acute effect of moclobemide on melatonin biosynthesis was not affected by chronic moclobemide administration. The observed difference in the chronic effects of irreversible and reversible selective MAO-A inhibitors on melatonin biosynthesis could have clinical implications.

Animals↗
PubMed1994

A fatality due to flurazepam.

A fatality attributed to suicidal ingestion of up to 2.2 grams of flurazepam is described. The deceased was a 52-year old female with a history of depression and suicidal attempts. No significant pathology was found at autopsy. Full toxicological analyses detected only flurazepam and metabolites in her tissues. The concentrations of flurazepam in femoral blood, liver, bile, vitreous humor and urine were 5.5 mg/L, 130 mg/kg, 33 mg/L, 1.3 mg/L and 3.3 mg/L, respectively. Analysis of gastric contents showed 600 mg of flurazepam. Desalkylflurazepam was also detected in blood, liver, bile and vitreous, but at much lower concentrations than the parent compound.

Chromatography, Gas↗
PubMed1992

A death involving probenecid.

A death following deliberate ingestion of approximately 75 g of probenecid in a 36-year-old man is described. Tissue concentrations of probenecid were highest in serum (710 mg/L) and liver (550 mg/kg). Probenecid was also detected in vitreous and bile. Ethanol was also detected in blood at 0.13 g/100 mL.

Adult↗
PubMed1991

The response of the pineal melatonin biosynthesis to the selective MAO-A inhibitor, clorgyline, in young and middle-aged rats.

1. Clorgyline increased pineal melatonin and N-acetylserotonin (NAS) and decreased 5-hydroxyindoleacetic acid (5-HIAA) content in 3 and 12 months of age male Sprague-Dawley rats kept under 12:12 h light: dark schedule. Exposure to light for 24 h before clorgyline administration resulted in additional elevation of NAS and melatonin. NAS and melatonin levels after clorgyline injections were significantly higher while 5-HIAA levels were significantly lower in young than in middle-aged rats. 2. The 5-HIAA/5-HT ratio (index of monoamine oxidase activity) was higher in middle-aged than in young rats suggesting the lesser degree of clorgyline-induced inhibition of MAO-A in old than in young rats. 3. It is suggested that melatonin response to a single dose of the selective MAO-A inhibitor might be used for the assessment of the aging changes of the rat (and human) pineals.

Aging↗
PubMed1991

Effect of ageing on melatonin synthesis induced by 5-hydroxytryptophan and constant light in rats.

1. This paper describes the effect of the serotonin precursor 5-hydroxytryptophan (5-HTP) on pineal melatonin synthesis young and old rats. 2. 5-HTP itself increased pineal melatonin levels in old rats but did not change melatonin concentrations in young rats kept under 12 hr/12 hr light/dark conditions. 3. After continuous exposure to light for 72 hrs, 5-HTP induced a significant increase in melatonin levels in young rats but did not change the 5-HTP effect on melatonin in old animals. 4. These results are discussed in consideration of previous reports of altered beta-receptor up-regulation by light in old animals, and suggest that the age-related decrease in melatonin synthesis is not entirely related to changes of the enzymatic machine for melatonin synthesis.

5-Hydroxytryptophan↗
PubMed1990

Serotonergic effects of isatin: an endogenous MAO inhibitor related to tribulin.

A study of the acute effects of isatin, an endogenous MAO inhibitor related to tribulin, on rat brain serotonergic function was undertaken. A single dose of isatin significantly increased 5-HT concentrations in the hypothalamus and cortex but did not significantly alter 5-HIAA concentrations. Synaptosomal 5-HT uptake was unaffected but there was a trend for the number of 3H-ketanserin binding sites was to be decreased. The results of the study are discussed in terms of the relationship of isatin to tribulin and their possible causal role in stress.

Animals↗
PubMed1990

High-affinity platelet [3H]LSD binding is decreased in panic disorder.

Platelet [3H]LSD binding was measured in 15 patients with panic attacks and 15 controls. The mean (+/- SD) Bmax values of the patients (14.1 +/- 6.3 fmol/mg protein) and of the controls (18.5 +/- 4.7 fmol/mg protein) were significantly different (P less than 0.05, Mann-Whitney U-test). Mean (+/- SD) values of Kd for the patients (0.55 +/- 0.34 nM) and for the controls (0.51 +/- 0.12 nM) were not significantly different (P greater than 0.1, Mann-Whitney U-test). The results are discussed in terms of a serotonergic hypothesis of the aetiology of panic disorders.

Adult↗
PubMed1990

Urinary 6-sulphatoxy melatonin levels within the menstrual cycle and in patients with premenstrual syndrome.

The present investigation examined the production of urinary 6-sulphatoxy melatonin (aMT.6S) during the early follicular and late luteal (premenstrual) phases in healthy, normal women and in patients with premenstrual syndrome (PMS). There was no significant difference in levels of aMT.6S on either day 6 or 26 of the menstrual cycle between control subjects and those with PMS. There also was no significant change in urinary aMT.6S levels within the menstrual cycle. These findings do not support an involvement of melatonin in the development of PMS symptomatology and are not supportive of the proposed role of melatonin in regulating ovulation in humans. However, our analysis of 12-hr urine samples may have been insensitive to small, yet possibly biologically significant, changes in the amplitude and period of melatonin excretion during the early hours of the morning.

Adult↗
PubMed1990

A portable light source for bright light treatment.

A novel, portable, inexpensive bright light source is described. This unit, which has been demonstrated to exhibit physiological effects similar to those of the more conventional light boxes, offers a less restrictive home treatment for patients with seasonal affective disorder and sleep disorders.

Adult↗
PubMed1990

Pharmacokinetic and pharmacodynamic effects of a single nocturnal dose of alprazolam.

Six healthy volunteers participated in a study of the pharmacokinetic and psychomotor effects of a single dose of 2 mg of alprazolam compared to placebo when given at night. Alprazolam reached a maximum concentration in the plasma between 0.5 and 2.5 h after the dose. It was extensively distributed to the tissues as shown by the large apparent volume of distribution (1.42 l/kg) and slowly eliminated (t1/2 = 13.7 h). Significant impairment of choice reaction time occurred 1 and 11 h after the dose of alprazolam compared to placebo. Critical flicker fusion was also impaired after alprazolam but the difference from the placebo administration did not reach significance.

Administration, Oral↗
PubMed1990

Plasma concentrations of melatonin in panic disorder.

Nocturnal plasma melatonin concentrations were measured in seven patients with panic disorder and eight healthy control subjects. The five patients who had never received psychotropic medication had significantly greater melatonin concentrations from 4:00 a.m. to 7:00 a.m. than the control subjects. In addition it is possible that a phase delay occurred in these unmedicated patients. The findings are discussed in terms of previous studies showing increased melatonin in manic patients and the effect of intense stress on melatonin synthesis. The two patients who had been medication free for only 1 week showed a decreased melatonin rhythm, which is consistent with previous findings in medicated patients.

Adult↗
PubMed1989

Quantal melatonin suppression by exposure to low intensity light in man.

Plasma melatonin concentrations were examined following three relatively low intensities of artificial light. Six normal, healthy control subjects were all exposed to (a) 200 lux, (b) 400 lux and (c) 600 lux for a three hour duration from midnight to 0300 h. Blood was also collected on a control night where light intensity was less than 10 lux throughout. Significant suppression of melatonin was observed following light of 400 lux and 600 lux intensity when compared to the control night (p less than 0.05; Mann-Whitney U-test). 200 lux light did not produce a statistically significant melatonin suppression when compared with control samples. Each light intensity produced its own individual maximal melatonin suppression by one hour of exposure. Increased duration of exposure to the light had no further influence on melatonin plasma concentrations. These data confirm a dose response relationship between light and melatonin suppression, and indicate that there is no reciprocal relationship between the effects of light intensity and the duration of exposure on maximal melatonin suppression in man.

Adult↗
PubMed1989

Platelet serotonin uptake in panic disorder patients: a replication study.

Platelet serotonin uptake was measured in 29 patients with DSM-III panic disorder or agoraphobia with panic attacks and compared to values obtained in 23 controls. Both the affinity constant (Km) and the maximal rate of uptake (Vmax) were determined in a buffered medium using 14C-serotonin. Patients and controls did not differ significantly with respect to age or Km values. A statistically significant difference was observed for Vmax (mean +/- SD = 65 +/- 22 pmol/10(8) platelet/min in patients vs. 44 +/- 13 pmol/10(8) platelets/min in controls). This finding suggests an overactivity of peripheral serotonergic function in panic disorder, which may also imply a similar dysfunction centrally.

Adolescent↗
PubMed1989

Human melatonin response to light at different times of the night.

Normal control subjects were examined on three separate occasions with light of sufficient intensity to suppress nocturnal plasma melatonin concentrations. One hour of light was given at each of the following times: (a) 2100-2200h; (b) midnight to 0100h; (c) 0400-0500h. Melatonin synthesis was just becoming apparent at 2100h. There was significant suppression of melatonin by light when given at midnight-0100h and 0400-0500h, but not when light was given at 2100-2200h. In each case following light, melatonin synthesis was shown to resume, even after light applied in the second half of the dark period (0400-0500h). A second experiment was undertaken to examine a possible "rebound" in melatonin levels following light given at 2100-2200h. Six further control subjects were exposed to light at this time, and plasma melatonin levels were measured until 0400h. No rebound in melatonin concentrations was observed. These results are compared with other studies of melatonin response to evening light exposure.

Adult↗
PubMed1989

Lack of effect of the antidepressant compound bupropion on pineal indoleamines.

The effects of the antidepressant compound bupropion were studied on rat pineal indoleamines. A pharmacologically relevant dose of bupropion either acutely (20 mg/kg) or chronically (20 mg/kg/day for 12 days) had no significant effect on pineal melatonin synthesis or other pineal indoleamine concentrations. The significance of this finding is discussed in relation to the lack of effect of bupropion on beta-adrenergic receptors.

Animals↗