Dantrolene sodium or dantrolene1 is 1-[5-(nitrophenyl)furfurylidene] 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.

Benserazide, (±)-DL-seryl-2-(2,3,4-trihydroxybenzyl)hydrazine, and carbidopa, (−)-L-α-hydrazino-3,4-dihydroxy-α-methylbenzenepropanoic acid, are inhibitors of extracerebral aromatic L-aminoacid decarboxylase (dopa decarboxylase). Combinations of benserazide and levodopa1 (1:4) or carbidopa and levodopa2 (1:10) are used in the treatment of Parkinson’s disease, both to treat new patients and as replacements for levodopa alone. Like levodopa, they appear to have little influence on the disease process, and their role in the long-term management of Parkinsonism is symptomatic and palliative.

Synopsis: Metoclopramide 1 , 4-amino-5-chlorO’2-methoxy-N-(2-diethyl-aminoethyl) benzamide, is advocated for use in gastro-intestinal diagnostics, and in treating various types of vomiting and a variety of functional and organic gastro-intestinal disorders.

Although longer‐term adaptive changes in receptor sensitivity may better explain the delayed onset of action of antidepressants, the mechanism based on acutely elevated noradrenaline (NA) and serotonin (5‐HT) synaptic levels remains the basis for new drug design. The dual action concept, which postulates that effects on both NA and 5‐HT are more advantageous than a selective action on serotonin reuptake (SSRI), has been used to design new antidepressants such as venlafaxine and mirtazapine. Both drugs enhance NA and 5‐HT neurotransmission with little affinity for receptors mediating tricyclic‐like side effects. Mirtazapine, the prototype noradrenergic and specific serotonergic antidepressant (NaSSA), specifically enhances 5‐HT, neurotransmission and blocks 5‐HT2 and 5‐HT3 receptors, and in contrast to venlafaxine lacks SSRI‐like and adverse cardiovascular side effects. The unique pharmacological action of mirtazapine is a result of implementation of two concepts: dual action as a basis of efficacy combined with receptor‐specific action as a basis of tolerability.

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ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTProspects for Improved AntidepressantsC. L. E. Broekkamp, D. Leysen, B. W. M. M. Peeters, and R. M. PinderCite this: J. Med. Chem. 1995, 38, 23, 4615–4633Publication Date (Print):November 1, 1995Publication History Published online1 May 2002Published inissue 1 November 1995https://pubs.acs.org/doi/10.1021/jm00023a001https://doi.org/10.1021/jm00023a001research-articleACS PublicationsRequest reuse permissionsArticle Views530Altmetric-Citations84LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts

AbstractAntidepressant drugs have unequivocally altered the short‐term outcome of depressive illness and reduced considerably the risk of morbidity. Their influence upon the chronic course of depression or upon the excess mortality associated with depressive illness is less easy to quantify. Nevertheless, the benefits of effectively treating depression far outweigh the considerable risks of leaving depressed patients inadequately, inappropriately or untreated. Most antidepressants currently available have broadly equal efficacy, although some drugs may be more appropriate in certain types of patient, when particular symptoms are prominent or when a particular side‐effect is undesirable.Antidepressants vary in their side‐effect profiles, and the newer non‐tricyclic drugs appear to offer a reduced risk of anticholinergic and cardiovascular effects. All of the newer drugs carry additional adverse effects, however, leading in the cases of zimeldine and nomifensin to withdrawal from the market and with mianserin to controls on prescription. Analysis of overdosage data indicates that the greatest risk of any antidepressant is fatality upon overdosage, the numbers of which far exceed fatalities from adverse effects. It is suggested that any assessment of the overall benefitsand risks of antidepressant drugs should include not only risks at therapeutic dosage but also the dangers of overdosage.

Tricyclic antidepressants and monoamine oxidase inhibitors are presumed to act rapidly to elevate synaptic levels of norepinephrine (NE) and serotonin (5-HT) by inhibiting uptake and metabolism, respectively. Synaptic levels of NE, how-ever, are not controlled entirely by reuptake and metabolic processes, but are under the additional influence of a negative feedback inhibition mediated by an agonist action of NE itself upon α2-adrenoceptors located presynaptically on the noradrenergic nerve terminal (Timmermans and van Zwieten 1982). Antagonism of these so-called autoreceptors leads to enhancement of the release of NE from its storage sites in the nerve terminal and thereby to a situation akin to that following uptake inhibition. α2-Autoreceptors have been demonstrated to exist at almost all noradrenergic axons where postsynaptic α-adrenoceptors are known to occur, and they are widely distributed in the brain, particularly in the cortex. The possibility that α2-autoreceptor antagonism might lead to antidepressant properties has stimulated the development of a number of putative therapeutic agents, which vary widely in their potency and selectivity (Pinder 1985 a, b).

Fifty elderly depressed patients were randomly assigned to double-blind treatment, using a flexible dose schedule, with either mianserin 20-60 mg or imipramine 75-150 mg. Medication was continued for four weeks. Eleven patients withdrew from the study. At the end of treatment there were no significant differences between mianserin and imipramine in antidepressant efficacy. A significantly greater number of side-effects occurred in the imipramine group (dry mouth, days 7 and 14; faintness, dizziness, weakness, day 21). When treating elderly depressed patients mianserin may be preferred to imipramine because of a lower incidence of induced side-effects.

Synopsis: Rimiterol1 is erythro-(3,4-dihydroxyphenyl)-2-piperidyl-methanol hydrobromide, and is a catecholamine. It is a selective β2-adrenoreceptor agonist, but is not effective as a bronchodilator by the oral route of administration. Rimiterol is available at present as an aerosol, though preliminary studies suggest that it may be of value in the intravenous therapy of severe asthma.

Sodium valproate1 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 γ-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 the treatment of epileptic patients.

Maprotiline1, 1-(3-methylaminopropyl) dibenzo(b,e) bicyclo (2.2.2) octadiene, is a tetracyclic drug, distinguished from conventional tricyclic antidepressants only by the rigid flexure of itsmolecular skeleton. In contrast to amitriptyline or imipramine, maprotiline has sedative and tranquillising properties in animals, appears to have negligible effects on the cardiovascular system in man, and does not influence the central metabolism of 5-hydroxytryptamine. It is indicated for use in the treatment of all types of mental depression or depressive mood disorders, but seems to offer no compelling advantages over the tricyclic antidepressants.

Synopsis:Tri-potassium di-citrato bismuthate1 is a complex bismuth salt stable in colloidal form advocated for the treatment of peptic ulcer. Preliminary placebo-controlled trials in small numbers of ambulant patients with endoscopically proven peptic ulcer, strongly suggest that the compound accelerates the rate of healing of gastric and duodenal ulcer within 4 weeks of treatment. However, trials involving larger numbers of patients followed-up for longer periods are required before a clear verdict on the efficacy of tripotassium di-citrato bismuthate in gastric and duodenal ulcer can be given. There are no reliable data on the effect of the drug on ulcer recurrence rate.

Hydrocortisone 17-butyrate1 is a new non-fluorinated topical corticosteroid for use in psoriasis, eczema and other inflammatory dermatoses. In double-blind paired comparisons with other topical corticosteroids, the efficacy of hydrocortisone 17-butyrate 0.1% has generally been indistinguishable from that of triamcinolone acetonide 0.1%, fluocinolone acetonide 0.025% or betamethasone 17-valerate 0.1% in patients with eczema or psoriasis.