[Changes in the circadian rhythm of respiratory activity in "depressive" rats as affected by tricyclic antidepressants]

[Changes in the circadian rhythm of respiratory activity in "depressive" rats as affected by tricyclic antidepressants] At chronic administration imipramine (10 and 25 mg/kg) and amitriptyline (10 mg/kg) shift the acrophase of the circadian rhythm of the rest-activity cycles in rats for a later time of the day. On the contrary, repeated injections of reserpine led to the rhythm acrophase shift for an earlier time and this effect is less pronounced against the background of the antidepressants. The effects of imipramine and amitriptyline are more distinct in the animals which exhibit signs of "depressiveness" in the open field and are more sensitive to the agents according to the forced swimming test. Journal ISSN: 0014-8318 Issue: 51-3 (1988 May-Jun) Pages: 5-8

Improving depression severity assessment--I. Reliability, internal validity and sensitivity to change of three observer depression scales.
Improving depression severity assessment--I. Reliability, internal validity and sensitivity to change of three observer depression scales. The Hamilton Depression Scale (HAMD) is the most commonly used scale for depression severity assessment and for antidepressant treatment evaluation. Alternative scales have been proposed by Bech and Rafaelsen (BRMS) and by Montgomery and Asberg (MADRS) to try to overcome the shortcomings of HAMD: they are based on different concepts of severity and different scaling procedures. Comparisons with respect to reliability, validity and ability to detect change have been performed using these scales in different samples. The BRMS proved superior. This result makes it necessary to question the usual procedure of testing the efficacy of antidepressants by means of HAMD alone. Problems in defining the severity of depression and in testing the validity of severity scales are discussed. Journal ISSN: 0022-3956 Issue: 22-1 (1988) Pages: 3-12

Vardenafil (Levitra) for erectile dysfunction: a systematic review and meta-analysis of clinical trial reports.
Vardenafil (Levitra) for erectile dysfunction: a systematic review and meta-analysis of clinical trial reports. Trials of the efficacy and safety of vardenafil in the treatment of male erectile dysfunction (ED) were meta-analysed. All available databases were searched (January 1, 2001-November 30, 2003). Trials were eligible if they included men with ED, compared vardenafil with placebo, were randomized, were at least of 12 weeks duration, and assessed clinically relevant outcomes. Two reviewers independently evaluated study quality and extracted data in a standardized fashion. Nine trials (6809 men) met the inclusion criteria. In results pooled from seven fixed-dose trials, vardenafil increases the Erectile Function domain of the International Index of Erectile Function questionnaire by 6.18 units (weighted mean difference (WMD)). Vardenafil also increases the percentage of erections firm enough to allow vaginal penetration (WMD: 26) and the percentage of sexual attempts that were successful per participant (WMD: 29.8). The percentage of men agreeing with the statement that @apos;the treatment they have been taking over the past 4 weeks improved their erections@apos;, is also in favour of vardenafil (relative risk (RR): 3). These efficacy variables appeared greater at higher doses, although there are no significant differences between 10 and 20 mg dose. The same results were extracted for the two flexible @apos;as needed@apos; dosing trials. Discontinuations are greater at the vardenafil groups compared to placebo (RR: 2.25). Specific adverse events with vardenafil included flushing, dyspepsia, headache, and rhinitis. Vardenafil was not significantly associated with serious cardiovascular events or death. Vardenafil, in all treatment regimens, shows to possess superior efficacy to placebo in the treatment of patients with erectile dysfunction. More data is needed on patients@apos; subgroups. Journal ISSN: 0955-9930 Issue: 16-6 (2004) Pages: 470-8

The effects of nonsteroidal anti-inflammatory drugs on blood pressures of patients with hypertension controlled by verapamil.
The effects of nonsteroidal anti-inflammatory drugs on blood pressures of patients with hypertension controlled by verapamil. BACKGROUND: Nonsteroidal anti-inflammatory drugs may attenuate the antihypertensive effects of diuretics, beta-blockers, angiotensin-converting enzyme inhibitors, central alpha-agonists, and other vasodilators. Their effects on the antihypertensive efficacy of calcium channel blockers are inadequately studied in small numbers of patients but appear to be minimal. METHODS: A three-phase, randomized, double-blind, placebo-controlled multicenter study included 162 patients aged 18 to 75 years with essential hypertension. After diastolic blood pressure was controlled to 90 mm Hg or less with once-daily verapamil hydrochloride, patients received ibuprofen, naproxen, or placebo matching capsules for 3 weeks, and blood pressure, heart rate, weight, and adverse effects were evaluated. A general linear model with 95% confidence intervals was used to compare each nonsteroidal anti-inflammatory drug treatment group with the placebo group. RESULTS: No significant differences in sitting, standing, or supine blood pressure were noted with naproxen or ibuprofen compared with placebo. The percentages of patients in each treatment group with increases of 10 mm Hg or more in either systolic or diastolic blood pressure were similar. Statistically significant increases in weight were seen with both nonsteroidal anti-inflammatory drug therapies. Changes in pulse rate were not significant. The incidence of adverse effects was similar across all three treatment groups. CONCLUSIONS: The addition of naproxen or ibuprofen to the treatment of hypertensive patients in whom blood pressure is controlled by once-daily verapamil does not cause an increase in blood pressure. Verapamil may therefore offer considerable advantages in maintaining control of blood pressure in patients who regularly receive nonsteroidal anti-inflammatory drug therapy. Journal ISSN: 0003-9926 Issue: 155-10 (1995) Pages: 1049-54

Potency, selectivity, and consequences of nonselectivity of PDE inhibition.
Potency, selectivity, and consequences of nonselectivity of PDE inhibition. Phosphodiesterases (PDEs) play a decisive role in cyclic nucleotide-mediated intracellular signaling. As PDEs are expressed in a variety of tissues, selectivity is a prerequisite for a therapeutically applicable PDE inhibitor. Sildenafil, vardenafil, and tadalafil are selective for PDE5, with vardenafil exhibiting the highest potency and minimal inhibition of other PDEs, with the exception of PDE6. Tadalafil is extremely selective for PDE5, but also potently inhibits PDE11, an enzyme with unknown physiological function. As PDE1 is expressed in the brain, myocardium, and vascular smooth muscle cells, nonselectivity with respect to this enzyme (selectivity: tadalafil>vardenafil>sildenafil) may result in vasodilation and tachycardia. Inhibition of PDE6 (selectivity: tadalafil>vardenafil congruent with sildenafil), which is expressed only in retina and functions in visual transduction, can transiently disturb vision. PDE5 inhibitors may also indirectly inhibit PDE3 by increasing cyclic guanosine monophospate levels, thereby elevating heart rate and vasodilation while inhibiting platelet aggregation. Journal ISSN: 0955-9930 Issue: 16 Suppl 1- (2004) Pages: S11-4

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