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Biomedical subjects

I M McIntyre

Publications and source records attributed to I M McIntyre.

At least 37 records · Page 2Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Serotonin in panic disorder: platelet uptake and concentration.

Platelet serotonin uptake and platelet serotonin concentrations were measured in 17 patients (5 males, 12 females) with panic attacks and 15 controls (8 males, 7 females). Higher Vmax values were found in the patient group compared with controls (65 +/- 7 vs. 47 +/- 3 pmol/10(8) platelets/min; p less than 0.05) while the affinity constant Km was not significantly different (0.6 +/- 0.1 vs. 0.5 +/- 0.1 microM). Platelet serotonin concentrations were not significantly different between the two groups (38 +/- 4 vs. 41 +/- 4 ng/10(8) platelets). These results confirm our earlier finding of increased serotonin uptake in patients with panic attacks and suggest that platelet serotonin levels are normal.

Adult↗

Human melatonin suppression by light is intensity dependent.

Five intensities of artificial light were examined for the effect on nocturnal melatonin concentrations. Maximum suppression of melatonin following 1 hr of light at midnight was 71%, 67%, 44%, 38%, and 16% with intensities of 3,000, 1,000, 500, 350, and 200 lux (lx), respectively. In contrast to some previous reports, light of 1,000 lx intensity was sufficient to suppress melatonin to near daytime levels, and intensities down to 350 lx were shown to significantly suppress nocturnal melatonin levels below prelight values. On the basis of these data, it is suggested that when examining the melatonin sensitivity of patient groups (such as bipolar affective disorders) to artificial light, an appropriate light intensity should be established in each laboratory. Light of less intensity (e.g., 200-350 lx) may be more suitable to dichotomize patient groups from control subjects.

Adult↗

Treatment of seasonal affective disorder with light: preliminary Australian experience.

Six patients with a history of Seasonal Affective Disorder (SAD) were treated with bright artificial light. Patients presented with at least two consecutive years of loss of energy, difficulty in working, loss of interest in activities, difficulty in concentrating, increased somnolence, over-eating (carbohydrate craving) and depressed mood. All received seven consecutive days of full-spectrum bright light with an intensity greater than 2,500 lux at a distance of three feet. Evening exposure for two hours resulted in significant clinical improvement. The main improvements were a return to normal sleeping patterns, a reduction in eating habits, improved energy level, a desire to continue with interests and activities and an improvement in mood. Possible mechanisms for the clinical effects of bright light treatment are discussed.

Australia↗

Serotonin and panic disorders: a review of clinical studies.

The revision of psychiatric diagnostic criteria by DSM-III has emphasised the central importance of panic attacks for the diagnosis of anxiety disorders. Since the introduction of this classification, there has been a re-evaluation of the role of major neurotransmitters as causal factors in anxiety disorders. The evidence for serotonergic hyperactivity in panic disorders is supported by the efficacy of specific serotonin reuptake blockers and 5HT2 receptor antagonists in the treatment of the condition. In addition neuroanatomical studies and positron-emission transaxial tomographic scanning are also consistent with a key role for serotonin in panic disorder. Clinical evidence of serotonin dysfunction has been sought using the blood platelet, a putative model of central serotonergic neurons. Studies of 3H-imipramine binding in platelets are equivocal, but most find no difference between patients and controls. On the other hand platelet serotonin uptake is significantly elevated in panic patients compared to controls. The reasons for the difference between two reputed markers of presynaptic serotonergic function is explored. The prolactin response to intravenous tryptophan administration is regarded as a functional correlate of central serotonergic neurons. Panic disorder patients and controls were not different in one study using this test. Serotonin concentrations in panic patients may be abnormal compared with appropriate controls. Replication of these preliminary data are necessary to confirm serotonergic dysfunction and to elucidate the interaction with other neurotransmitters, with clear implications for pharmacotherapy.

Fear↗

Plasma melatonin levels in affective states.

Melatonin is a major endocrine product of the pineal gland. It is produced at night when noradrenaline acts on beta-adrenergic receptors to stimulate enzymes which catalyse the formation of melatonin from serotonin. It is believed by some that nocturnal melatonin levels reflect beta-receptor function. The melatonin rhythm is also thought to be an indication of circadian rhythmicity. The nocturnal production of melatonin was studied in patients with depression and panic disorder and in control subjects. Midnight concentrations of melatonin in eleven depressed patients were significantly lower than 18 control subjects (27.1 +/- 5.1 pg/ml compared with 51.6 +/- 4.1 pg/ml; p less than 0.02, t-test). These data support previous reports of reduced melatonin synthesis in depressive illness. In the first report of patients with panic disorders, significantly lower midnight levels of melatonin were found compared with controls (28.4 +/- 6.4 pg/ml versus 51.6 +/- 4.1 pg/ml, p less than 0.02, t-test). In subsequent investigations this finding was confirmed, measuring melatonin levels over the initial phase of synthesis (i.e. 20h00 to 24h00). In these samples the melatonin rhythm also seemed to be delayed. These findings are discussed in terms of beta-receptor function and circadian rhythm alterations in affective disorders.

Adolescent↗