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Biomedical subjects

H M Calil

Publications and source records attributed to H M Calil.

At least 37 records · Page 2Linked to original sources
PubMed1983

Effects of desmethylimipramine on plasma norepinephrine, pulse, and blood pressure.

We followed the effects of a tricyclic antidepressant selective for norepinephrine (NE) uptake inhibition, desmethylimipramine (DMI), on blood pressure, heart rate, and plasma NE level in healthy subjects. After a single oral dose of 100 mg DMI, supine systolic and diastolic blood pressure and supine and upright heart rate rose, and there was an increment in heart rate with standing. After long-term low doses of the drug (mean daily dosage 67.5 mg), the upright level and increment with standing in plasma NE also rose. Supine NE levels also rose after the long-term higher dose (mean daily dosage 125 mg). No differences in any measures were detected between the short- and the two long-term dose levels of DMI. Our findings suggest that NE uptake inhibition induces physiologic elevation of NE concentration in the sympathetic neuroeffector region. A similar effect at synapses in the CNS might be involved in the mechanism of antidepressant action.

Adult↗
PubMed1982

Alteration of norepinephrine metabolism with desipramine and zimelidine in depressed patients.

Twelve patients with a major affective disorder were treated during the depressed phase of their illness with desipramine hydrochloride and/or zimelidine hydrochloride, and urinary excretion rates of norepinephrine and its major metabolites were examined. During treatment with desipramine, daily urinary excretion of norepinephrine, 3-methoxy-4-hydroxyphenylglycol (MHPG), and vanillylmandelic acid was reduced, but urinary normetanephrine excretion was not significantly changed. In all patients, the proportion of urinary norepinephrine metabolites represented by normetanephrine was increased during desipramine treatment. Independent of treatment outcome, desipramine seemed to decrease total formation and metabolism of norepinephrine, which was reflected in decreases in the excretion rate of the catecholamine and its metabolites. These results are consistent with known actions of desipramine on the disposition of norepinephrine and represent alterations in the rate of norepinephrine formation and metabolism, resulting from inhibition of norepinephrine reuptake. Zimelidine, a new antidepressant, which is a relatively specific serotonin-uptake inhibitor, significantly reduced only urinary MHPG excretion without appearing to alter "whole-body" norepinephrine turnover. This effect of zimelidine on norepinephrine metabolism was unexpected. Current and previous findings concerning clorgyline, a relatively specific monoamine oxidase A inhibitor, suggest that three pharmacologically distinct classes of antidepressants, norepinephrine and serotonin-reuptake and monoamine oxidase type A inhibitors, all reduce central norepinephrine turnover in depressed patients.

Antidepressive Agents↗
PubMed1982

Active metabolites of imipramine and desipramine in man.

Active hydroxy metabolites of imipramine (IMI) and desipramine (DMI) have been quantified in plasma and cerebrospinal fluid (CSF) from patients at steady-state. In plasma of prepubescent boys and adults the concentration of unconjugated 2-hydroxyimipramine is only 15% to 25% that of IMI; 2-hydroxydesipramine (OH-DMI) concentration, however, is usually 50% that of DMI and in some cases OH-DMI is the predominant compound. In CSF from adult patients the ratio of concentrations of OH-DMI/DMI is higher than in plasma. Judging from the CSF/plasma ratio 12% of DMI exists in the free form at steady state, whereas 16% of OH-DMI is free (P less than 0.02). There is no evidence for saturation of hydroxylation within the therapeutic dose and concentration ranges investigated. On the basis of a steady-state OH-DMI/DMI ratio of less than 1/30 in plasma 5% of the population studied could be classified as deficient DMI hydroxylators. This in the same as the incidence of deficient debrisoquine hydroxylators reported in other populations.

Adolescent↗
PubMed1982

Zimelidine and norzimelidine protein binding measured by equilibrium dialysis and cerebrospinal fluid.

Steady-state concentrations of a new antidepressant, zimelidine (ZIM), and its active metabolite, norzimelidine (NZIM), were measured in plasma and cerebrospinal fluid (CSF) in eight depressed patients. Free drug, as calculated from the ratio of CSF to plasma concentration, of ZIM was 8.4 +/- 1.8% and of NZIM was 18.3 +/- 2.8%. Equilibrium dialysis (ED) of plasma from the same patients on placebo yielded free fractions of 8.6 +/- 2.2% and 28.1 +/- 3.4% for the two compounds. alpha 1-Acid glycoprotein (alpha a-AG) was also measured in the same samples. Variation in free drug using either method was not great, but did modestly correlate with alpha 1-AG concentration in six of the eight patients in whom simultaneous placebo measures were available. Our results indicate that measurements in plasma or of free drug dependent on ED lead to erroneous conclusions regarding the proportion of free NZIM to ZIM. Considering the different potencies of the parent compound and active metabolite, this is an unusual problem.

Adolescent↗
PubMed1982

Alcohol-induced euphoria: alcoholics compared to nonalcoholics.

The affective responses of 24 alcoholics and 21 nonalcoholics were compared in a 2-hour free-drinking situation. At baseline the alcoholics were more dysphoric. During the drinking, the alcoholics reported no relief from the dysphoria but reported and displayed increases in positive mood. The magnitude of the positive affective response to alcohol was comparable in the two groups judged by most scales. The data offer little support for the hypothesis that alcoholics achieve a special euphoria from alcohol. Methodological problems in assessing alcohol-induced mood changes are reviewed.

Adult↗
PubMed1982

Lithium-induced male sexual impairment: two case reports.

Two cases of male sexual dysfunction associated with lithium therapy for major affective disorder, bipolar type I, are reported. One patient received a blind placebo substitution, with rapid disappearance of dysfunction. The second patient presented similar symptoms, which remitted spontaneously on continued lithium therapy. Since lithium is among the most effective and frequently used treatments for affective illness, such side effects, previously considered rare, may be expected to increase in frequency.

Adult↗
PubMed1981

Specific norepinephrine and serotonin uptake inhibitors in man: a crossover study with pharmacokinetic, biochemical, neuroendocrine and behavioral parameters.

Eight depressed patients with major affective illness were treated with both zimelidine, a selective serotonin-uptake inhibitor, and with desipramine, a selective norepinephrine uptake inhibitor, following a double-blind crossover design. At steady-state the active metabolite of zimelidine, norzimelidine, predominated in the CSF by a factor of 7 to 1 over parent drug. As predicted, even high concentrations of norzimelidine were not associated with decreased 3-methoxy-4-hydroxy-phenylglycol (MHPG) in the CSF. In the same individuals, desipramine concentrations were highly correlated with decreases of MHPG in the CSF. Despite specific effects on monoamine neurotransmitter systems which have been implicated in the control of neuroendocrine secretion, neither drug had consistent effects on plasma cortisol, luteinizing hormone, growth hormone or prolactin. Both drugs had a marked and unexpected common effect on the 24-hour rest-activity cycle. The excess activity during the normal rest period (0--700 hr.) which has been noted in severely depressed individuals was significantly reduced by both the serotonergic zimelidine and the noradrenergic desipramine. These findings suggest that effects on the rest-activity pattern may be a common pathway for antidepressant effect.

Adolescent↗
PubMed1981

Use of ECT with treatment-resistant depressed patients at the National Institute of Mental Health.

The authors review the use of ECT with nine seriously depressed patients at the National Institute of Mental Health over the past 8 years. Despite the patients' poor prior response to a variety of pharmacological treatments, only one patient failed to show a complete response to ECT. With most patients, improvement was quite rapid and dramatic, and all of the ECT responders were free of depression for at least 1 year after treatment. These results are consistent with previous studies; they deserve reemphasis now in light of recent controversies over ECT, including legislative and judicial attempts to restrict its use.

Adult↗
PubMed1979

Comparative pharmacokinetics of zimelidine and desipramine in man following acute and chronic administration.

Single dose and steady-state pharmacokinetics of zimelidine and desipramine were compared in eight depressed patients who were subjects in a double-blind crossover study. Within the same patient, there was no relationship between the pharmacokinetics of desipramine (pharmacokinetically similar to all other tricyclic antidepressants) and those of zimelidin, a bicyclic antidepressant. The weight-corrected dose of zimelidine gives a reasonable index of the concentration of its active metabolite norzimelidine, which predominates over zimelidine by a ratio of approximately 3 to 1. The variation in steady-state concentration of norzimelidine for a given dose of zimelidine in adults is about twofold and can be reduced by correcting for weight.

Adolescent↗
PubMed1979

Serum levels of neuroleptics measured by dopamine radioreceptor assay and some clinical observations.

A new dopamine radioreceptor assay was used to measure serum concentrations of neuroleptics during treatment of 58 patients. Results of this assay are expressed as chlorpromazine equivalents. Serum concentrations varied with different drugs, with extremely high levels in patients receiving thioridazine or mesoridazine. No detectable serum levels were found in 11 patients, probably either due to low drug doses or noncompliance in taking medication. Best results with the assay were obtained in the 22 patients treated with haloperidol. Serum concentrations of haloperidol were correlated with dose and were related to the Brief Psychiatric Rating Scale (BPRS) total pathology score, as well as to BPRS factor scores for thinking disturbance and paranoid disturbance. Serum concentrations of haloperidol were not different among patients with or without the presence of extrapyramidal symptoms or among patients receiving or not receiving concurrent antiparkinson medication.

Antipsychotic Agents↗
PubMed1979

Hydroxylated metabolites of tricyclic antidepressants: preclinical assessment of activity.

Studies investigating a possible relationship between the plasma concentration of tricyclic antidepressants and clinical response have measured only the tertiary and secondary amine forms of these drugs. The present study shows that the hydroxy metabolites of tricyclic antidepressants might also be active. Hydroxylated imipramine, desipramine, chlorimipramine, and nortriptyline inhibit the uptake of norepinephrine and serotonin into synaptosomes to the same extent as do their parent compounds. Hydroxylated nortriptyline and imipramine reverse or prevent reserpine-induced motor retardation and ptosis. Following chronic imipramine, significant steady-state concentrations of unconjugated hydroxylated metabolites are present in rat tissues including the cerebrospinal fluid. Accounting for steady-state concentrations of hydroxylated metabolites of tricyclic antidepressants in man may help to clarify whether there is a relationship between active drug concentration and clinical effect.

Animals↗
PubMed1978

Screening hallucinogenic drugs II. Systematic study of two behavioral tests.

The effects of hallucinogenic and nonhallucinogenic drugs were studied on two behavioral tests: (1) discriminated Sidman avoidance, using modified Bovet-Gatti profiles, which have been proposed as specific in detecting hallucinogenic activity and (2) a drug discrimination experiment. By the first method, the "hallucinogenic profile" was obtained with both hallucinogenic and nonhallucinogenic drugs and, at least as used here, was not a suitable screening method. In the drug discrimination experiment, data from the present study along with other available evidence suggest the potential value of this method for drug screening procedures.

Animals↗
PubMed1975

Screening hallucinogenic drugs: systematic study of three behavioral tests.

The effects of several hallucinogenic and non-hallucinogenic drugs have been studied on three behavioral tests proposed as useful indexes of hallucinogenic activity: "head-twitching" in mice, defecation in an open-field, and suppression of responding on a differential reinforcement of low rates (DRL) schedule of reinforcement. According to the original propositions, after administration of hallucinogenic agents the frequency of head-twitches would increase in mice, the defecation of rats in an open field would decrease without consistent change in ambulation, rearing and grooming, and the responding of rats on a DRL schedule would yield a typical cumulative record pattern. It was found that the head-twitch test was sensitive to mescaline and LSD-25, but not to delta9-THC or to myristicin and elemicin. Besides, the data on interobserver agreement suggested there is a high degree of subjectivity involved in assessing this response. In the open-field test, non-hallucinogenic drugs such as chlorpromazine and apomorphine fell into the hallucinogenic pattern proposed. In addition, the post-injection interval selected seemed to critically affect defecation scores. The DRL "hallucinogenic" pattern occurred nonspecifically after administration of hallucinogenic and non-hallucinogenic drugs. It was concluded that the three tests have limited value for screening purposes.

5-Hydroxytryptophan↗