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Biomedical subjects

R M Pinder

Publications and source records attributed to R M Pinder.

At least 37 records · Page 2Linked to original sources
PubMed1982

Monoamine metabolites in cerebrospinal fluid of depressed patients during treatment with mianserin or amitriptyline.

A group of 20 inpatients with moderate to severe primary affective disorder received 14 days of placebo treatment and were then randomly allocated to receive mianserin 10 mg 3 times daily or identical amitriptyline 25 mg 3 times daily for 1 week followed by 60 mg mianserin or 150 mg amitriptyline daily for a second week. Patients were rated for side-effects and depression (Hamilton Depression Scale) on days 0, 7, 14, 21 and 28. Probenecid 100 mg/kg was administered in 3 divided doses on days 13/14 and on days 27/28 of the trial, followed by collection of CSF. Blood samples for determination of antidepressant levels were collected on day 27. Both mianserin and amitriptyline produced a significant decrease in CSF levels of 3-methoxy-4-hydroxyphenylglycol (MHPG), but only amitriptyline significantly lowered CSF levels of 5-hydroxyindole-3-acetic acid (5-HIAA). Neither drug affected CSF levels of homovanillic acid (HVA). Both mianserin and amitriptyline produced significant but indistinguishable improvement in mean Hamilton scores over 2 weeks of treatment. There was no relationship between therapeutic response and either plasma antidepressant levels or pre-treatment CSF monoamine metabolite levels in his small group of patients. The reductions of CSF levels of metabolites of NA (MHPG) and 5-HT (5-HIAA) are consistent with the known effects of amitriptyline on amine uptake. Mianserin may reduce CSF MHPG levels as a result of its effects upon NA release and/or uptake, but it appears to be devoid of influence upon central 5-HT metabolism.

Adult↗
PubMed1982

A multicentre placebo-controlled trial comparing the efficacy of mianserin and chlordiazepoxide in general practice patients with primary anxiety.

In a double-blind multicentre trial in general practice, 144 patients with primary anxiety received daily treatment with mianserin or chlordiazepoxide, 30-60 mg, or placebo. There were no statistically significant differences in efficacy between the three treatments in the 106 patients who completed the 6-week trial. However, there was a substantial trend in favour of mianserin (P = 0.1), but not chlordiazepoxide, over placebo as assessed by the difference in overall improvement on the Hamilton Anxiety Scale. This trend may be clinically significant since more patients dropped out from the placebo group because of lack of effect or deterioration than did from the active treatment groups, particularly during the latter part of the trial. Side effects occurred to a similarly low extent with all treatments, except that mianserin caused more weight gain and, initially, more drowsiness than placebo, while placebo produced more nausea and vomiting. Taken together with the evidence from previous trials in patients with anxiety, these results support the notion that mianserin has anxiolytic properties.

Adolescent↗
PubMed1982

Mianserin.

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Animals↗
PubMed1981

[Predicted pharmacology of an antidepressant].

Pharmacological tests based on the reversal of effects induced by reserpine or reserpine-like drugs have been used extensively for the identification of potential antidepressants. The classical tests detect some of the antidepressants in addition to traditional tricyclics and monoamine oxydase inhibitors, but fail to identify other clinically effective antidepressants like mianserin and trazodone. New methods have therefore been developed including models based on reversal of various behavioural stereotypes of drug-induced effects. No single model is perfect, because all either detect drugs known not to be antidepressant (false positives) or, which is worse, fail to detect some clinically effective antidepressants (false negatives). The most reliable models involve reversal by antidepressants of the effects of bulbectomy in rats or selective suppression of REM sleep in cats, out neither is suitable for screening purposes. Neurochemical tests and receptor binding, like all tests for antidepressant activity, are fated to detect me-too drugs. Better and more relevant models must await a deeper understanding of the nature of depression.

Animals↗
PubMed1980

A double-blind group comparative trial of mianserin and diazepam in depressed outpatients.

In a double-blind trial in depressed outpatients, 80 subjects received either mianserin 30--80 mg daily or diazepam 15--40 mg daily, for 4 weeks. Most patients received 50--60 mg mianserin, or 25--30 mg diazepam, daily after the first week. Mianserin was significantly superior to diazepam in antidepressant efficacy from day 14 to the end of the trial, as measured by the Hamilton Rating Scale for Depression and the Beck Self-Rating Scale, and at day 28 as measured by the Clinical Global Impression. All three measures showed that the mianserin group started the trial with a significantly more severe degree of illness than the diazepam group, but this difference was already reversed by day 14. Side-effects were more frequent with mianserin treatment.

Adolescent↗
PubMed1980

A double-blind multicentre trial comparing the efficacy and side-effects of mianserin and chlorimipramine in depressed in- and outpatients.

Mianserin (60 mg daily) was compared with chlorimipramine (150 mg daily) in the treatment of 145 depressed in- and outpatients in four centres. The trial was double-blind and fully randomized. Both drugs were effective antidepressants. No significant differences in efficacy could be demonstrated by means of the Hamilton rating scale for depression, the Beck self-rating scale or the clinical global impression, for both in- and outpatients. Hypotension, dry mouth and tremor increased significantly more in inpatients with chlorimipramine than with mianserin. At the end of treatment weight gain was increased significantly more in outpatients after treatment with mianserin. No differences could be demonstrated between the drugs for other side-effects.

Adolescent↗
PubMed1980

Sleep-endocrine profile of the antidepressant mianserin.

The effects of mianserin, a tetracyclic antidepressant, on sleep stages and on the nocturnal secretion of cortisol, ACTH, growth hormone, prolactin and tryptophan were studied on 11 normal male volunteers in a double-blind, placebo-controlled study. Mianserin increased Stage 3 time (p less than 0.001) and Stage 4 time (p less than 0.01). It reduced the number of REM periods (p less than 0.001), the REM latency after sleep onset (p less than 0.01) and both the total and percentage REM time (p less than 0.05). A reduction in both the total sleep time (p less than 0.05) and the percentage of total time in bed (p less than 0.05) were the only significantly carry-over effects from the drug treatment period. No significant difference in any biochemical measurement was found between placebo and drug treatment.

Adult↗
PubMed1979

A controlled comparative trial of mianserin and diazepam in the treatment of anxiety states in psychiatric out-patients.

Forty psychiatric out-patients with primary anxiety entered a double-blind trial comparing 2 weeks of treatment with mianserin 30--60 mg daily or diazepam 15--30 mg daily, followed by 2 weeks of single-blind placebo administration. Both drugs were effective anti-anxiety agents, but mianserin was significantly superior in efficacy as measured by the Physician's Global Rating of Severity of Illness. No differences between treatments were apparent using the Hamilton Rating Scale for Anxiety. There was no significant differences in terms of side-effects and both drugs increased anticholinergic effects such as dry mouth, blurred vision and constipation over baseline values. With one exception in the mianserin group, all patients who entered placebo treatment became worse.

Adolescent↗
PubMed1977

Dantrolene sodium: a review of its pharmacological properties and therapeutic efficacy in spasticity.

Dantrolene sodium or dantrolene1 is 1([5-(nitrophenyl)furfurylidend] amino) hydantoin sodium hydrate. It is indicated for use in chronic disorders characterised by skeletal muscle spasticity, such as spinal cord injury, stroke, cerebral palsy and multiple sclerosis. Dantrolene is believed to act directly on the contractile mechanism of skeletal muscle to decrease the force of contraction in the absence of any demonstrated effects on neural pathways, on the neuromuscular junction, or on the excitable properties of the muscle fibre membranes. Controlled trials have demonstrated that dantrolene is superior to placebo in adults or children with spasticity from various causes, as evidenced by clinical assessments of disability and daily activities, and by muscle and reflex responses to mechanical and electrical stimulation. It is somewhat less effective in patients with multiple sclerosis than in those with spasticity from other causes. There has been a general clinical impression in controlled trials that dantrolene caused less sedation than would have been expected from therapeutically comparable doses of diazepam. In 2 controlled trials, there was no significant difference between dantrolene and diazepam in terms of reductions in spasticity, clonus, and hyperreflexia, but side-effects such as drowsiness and inco-ordination occurred significantly more frequently on diazepam. Long-term studies have indicated continuing benefit for patients taking dantrolene, though the incidence of side-effects has often been high and there has been a suggestion of exacerbation of seizures in children with cerebral palsy. Dantrolene may be of value in the medical treatment of spasm of the external urethral sphincter due to neurological and non-neurological disease, and animal studies suggest a potential use in the management of malignant hyperpyrexia. Chemical evidence of liver dysfunction may occur in 0.7 to 1% of patients on long-term treatment with dantrolene, with symptomatic hepatitis in 0.35 to 0.5% and fatal hepatitis in 0.1 to 0.2%. The drug commonly causes transient drowsiness, dizziness, weakness, general malaise, fatigue and diarrhoea at the start of therapy. Muscle weakness may be the principal limiting side-effect in ambulant patients, particularly in those with multiple sclerosis, and therapy could be hazardous in patients with pre-existing bulbar or respiratory weakness. The dosage of dantrolene has been fixed in most controlled trials, though long-term studies have indicated the need for individualisation of dosage. The initial dose is usually 25mg once daily, increasing to 25mg two, three or four times daily, and then by increments of 25mg up to as high as 100mg two, three or four times daily. The lowest dose compatible with optimal response is recommended.

Adult↗
PubMed1977

Sodium valproate: a review of its pharmacological properties and therapeutic efficacy in epilepsy.

Sodium valproate has a broad spectrum of anticonvulsant activity, but is structurally unrelated to conventional antiepileptic drugs. Its proposed mode of action is mediated through effects on the function of brain gamma-aminobutyric acid (GABA). However, the elevations in brain and cerebellar GABA, and the concomitant reductions in levels of cyclic guanosine monophosphate, occur in animals at dose levels which are unlikely to be achieved during treatment of epileptic patients.

Administration, Oral↗
PubMed1977

Doxepin up-to-date: a review of its pharmacological properties and therapeutic efficacy with particular reference to depression.

Doxepin is closely related in structure and general pharmacological properties to other tricyclic antidepressant drugs such as amitriptyline and imipramine. It combines antidepressant activity with a sedative effect and in this respect resembles amitriptyline, with which it shares a similar profile of clinical action. The mood elevating effect of doxepin appears to be similar to that of amitriptyline but is probably less marked than that of imipramine and in some studies has been slower to take effect than imipramine. At dosages which have achieved a similar overall response rate, doxepin tends to cause fewer or less troublesome side-effects than imipramine, amitriptyline or amitriptyline-prephenazine. The more marked sedative properties of doxepin make it more useful than imipramine in depressed patients with sleep distrubances and in depression associated with anxiety. The benzodiazepines remain the drugs of choice in anxiety states. but when anxiety is accompained by significant depression, doxepin is more effective than chlordiazepoxide or diazepam. Doxepin is usually well tolerated, and in particular by the elderly and those with cardiovascular disease. Side-effects are similar in nature to those of other tricyclic antidepressants, with dry mouth, drowsiness and constipation being the most common. Postural hypotension is uncommon. Although doxepin appears to cause fewer cardiovascular side-effects in usual therapeutic doses, it has an intrinsic cardiotoxicity on overdosage similar to other tricyclics.

Alcoholism↗
PubMed1977

Fenoprofen: a review of its pharmacological properties and therapeutic efficacy in rheumatic diseases.

Fenoprofen1 (dl-2-[3-phenoxyphenyl]propionic acid) is a new non-steroidal anti-inflammatory, antipyretic, analgesic agent advocated for use in rheumatoid arthritis, degenerative joint disease, ankylosing spondylitis and gout. Published data suggest that in rheumatoid arthritis, fenoprofen 2.4 g daily is comparable in effectiveness with moderate doses of aspirin (3.6 to 4 g daily), but generally causes fewer and milder side-effects at the dosages used. In published comparisons with other non-steroidal anti-inflammatory agents of the same chemical group, it is closely comparable with naproxen in effectiveness but tends to cause more minor side-effects than naproxen. However, as no one of the non-steroidal anti-inflammatory agents is the most suitable drug for all patients requiring such therapy, fenoprofen should be considered along with the other drugs of its type in the initial treatment of the arthritic patient. Fenoprofen has compared favourably with phenylbutazone in osteoarthrosis of the hips and with aspirin in osteoarthrosis of the shoulders, hips, knees and spine. Its exact place in the management of gout and ankylosing spondylitis remains to be determined.

Analgesics↗
PubMed1977

Hexoprenaline: a review of its pharmacological properties and therapeutic efficacy with particular reference to asthma.

Hexoprenaline1, N,N-[2-(3,4-dihydroxyphenyl)-2-hydroxyethyl] hexamethyl-enediamine, sulphate is a selective beta2-adrenoreceptor agonist which is active in man as a bronchodilator by the oral or intravenous routes and by inhalation. It is indicated for use in the treatment of bronchospasm associated with obstructive airways diseases, including asthma, bronchitis and emphysema. Clinical experience and double-blind studies have established that hexoprenaline is an effective bronchodilator. It major advantage over many other many other brochodilators of equal efficacy is its generally low production of side-effects, particularly tremor, palptitations, and tachycardia. In comparative trials, it has generally been rated as superior to orciprenaline or trimetoquinol, but comparisons with salbutamol have provided equivocal results. Oral hexoprenaline was superior to fenoterol as long-term maintenance therapy is asthma, principally because its somewhat lesser bronchodilatory effects were more than compensated for by a lesser incidence of side-effects.

Administration, Oral↗
PubMed1976

Characterisation of the mechanisms for hyperactivity induction from the nucleus accumbens by phenylethylamine derivatives.

A wide variety of phenylethylamine derivatives were injected bilaterally into the nucleus accumbens of rat following a nialamide pretreatment and hyperactivity was recorded. 2-Phenylethylamine was shown to induce a low intensity hyperactivity but the introduction of hydroxyl functions on to the phenyl ring at the 3- and/or 4-positions enhanced activity and m- and p-tyramine and dopamine each caused marked hyperactivity in the 3.4-25 mug dosage range. Methylation of one hydroxyl function reduced activity (3-methoxy-4-hydroxy- and 3-hydroxy-4-methoxy-phenylethylamine); 2(3,4-methylenedioxyphenyl) ethylamine was inactive. Agents with substitution of the side chain, such as noradreline, d-amphetamine and alpha-methyldopamine, were all shown to induce marked hyperactivity at doses of 1.6-25 mug. Alterations in the chain length markedly reduced activity (4-(3,4-dihydroxyphenyl) butylamine, 3,4-dihydroxybenzylamine). A variety of N-substituted compounds were shown to be potent inducers of hyperactivity from the nucleus accumbens (adrenaline, epinine, N-ethyldopamine, N-isopropyl-dopamine, isoprenaline) (0.2-25 mug). However, N-methyl-N-isopropyldopamine showed only weak activity and N,N-dimethyldopamine was inactive. All hyperactivity effects were shown to be dose-dependent. The hyperactivities induced by dopamine, noradrenaline and isoprenaline were each inhibited in a dose-dependent manner by subsequent injections of fluphenazine (1.25-25 mug) into the nucleus accumbens, although no reductions were recorded following similar injections of saline, solvent, 2% procaine, 50 mug propranolol or 50 mug piperoxan.

Animals↗