ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis and .beta.-adrenergic receptor blocking potency of 1-(substituted amino)-3-(4-indolyloxy)propan-2-olsShanaz M. Tejani-Butt and David J. BrunswickCite this: J. Med. Chem. 1986, 29, 8, 1524–1527Publication Date (Print):August 1, 1986Publication History Published online1 May 2002Published inissue 1 August 1986https://pubs.acs.org/doi/10.1021/jm00158a035https://doi.org/10.1021/jm00158a035research-articleACS PublicationsRequest reuse permissionsArticle Views134Altmetric-Citations10LEARN 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
A double‐blind comparison of doxepin versus desipramine was performed in carefully defined patients with research diagnoses of Primary Affective Disorder. While both drugs showed equal efficacy after 4 weeks, doxepin demonstrated a more rapid onset of action and surprisingly few side effects. Desipramine did not prove to be “activating” and did not worsen agitated depression. Although doxepin showed few autonomic side effects, it was nevertheless sedating, indicating that tricyclics with more anticholinergic effects are not necessarily more sedating drugs.
There is interest in knowing whether beta adrenergic antagonists or agonists, when administered systemically, can enter the brain to interact with central beta adrenergic receptors. To study this, the reduction in the radioactive content in the brain of rats after administration of (-)-[125I]iodopindolol (IPIN) by systemically administered beta agonists or antagonists was measured. Previous studies show that after the i.v. administration of IPIN the binding in vivo to various areas of the central nervous system has the characteristics expected of binding to beta adrenergic receptors. Of the antagonists tested, pindolol and butylpindolol showed potent interactions with beta receptors in both cortex and cerebellum whereas atenolol and practolol did not interact at doses up to 30 mg/kg. CGP-12177 showed moderate potency in inhibiting IPIN binding in vivo. We have shown previously that propranolol and alprenolol inhibit IPIN binding with high potency in cortex and cerebellum. At high doses, butoxamine, a beta-2 antagonist, reduced the binding of IPIN in the cerebellum but not in the cortex. Of the agonists tested, clenbuterol and prenalterol caused a significant dose-dependent reduction of the binding of IPIN, with clenbuterol being more potent. Isoproterenol, salbutamol, salmefamol and dobutamine had no effect. With the exception of CGP-12177, the affinity of the drugs for central beta adrenergic receptors measured in vitro was correlated significantly with their ability to inhibit IPIN binding in vivo whereas their degree of lipophilicity was not correlated significantly with potency in vivo. The inhibition of IPIN binding in vivo from brain areas can be used to evaluate whether drugs penetrate into brain and interact with central beta adrenergic receptors.
Interest in biogenic amine function in affective disorders has stimulated a variety of research strategies including the measurement of hormonal response to a variety of stimuli as an indirect method of investigating the integrity of aminergic function in clinically depressed patients. Apomorphine and levodopa are known to stimulate growth hormone release via a dopaminergic pathway in median eminence. Administration of these agents to groups of depressed patients and age, sex-matched normal control subjects did not indicate any significant abnormality in this dopaminergic system.
Tricyclic antidepressant plasma levels were measured in patients and healthy subjects after a single dose of desmethylimipramine (DM1) or imipramine (IMl) and after chronic dosing to steady states. Tricyclic plasma levels measured 24 hr after the single oral dose correlated with steady‐state plasma levels. In patients receiving DM1 there was a correlation (r = 0.97, n = 10) between 24‐hr and steady‐state DM1 levels, while in normal subjects receiving IMI the correlation was r = 0.92 (n = 20) between 24‐hr and steady‐state total tricyclic levels (IMI plus its metabolite, DMI). These results suggest the possibility that after a test dose of tricyclic antidepressant, a patient may be put on a “therapeutic” dosage regimen without delay.
