Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042571 (vertigo)
 7,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dihydroergocristine (DEC, CAS 17479-19-5) is a dihydrogenated ergot alkaloid with a potent dopaminergic activity that has been proved both in vitro and in vivo. Apart from its effect on the secretion of pituitary hormones, the following actions have been evidenced. It induces stereotyped behaviour and changes in the sleep-waking cycle, and reduces hypoxia-induced cerebral metabolic changes and emesis. The effect of DHEC on behaviour patterns has been studied in aged male rats in comparison with young animals. The acquisition of the active avoidance response in the shuttle-box test and the retention of the passive avoidance response in a step-through passive avoidance task were facilitated in aged rats by an acute treatment with DHEC. The effect on the acquisition and extinction of the pole-jumping performance after a single injection of DHEC at the beginning of the acquisition session was restricted to the first acquisition trial. A more potent effect on the acquisition of the shuttle-box response and on the retention of passive avoidance reaction was found in animals treated subchronically with DHEC. The latter animals also showed a facilitation of acquisition and an inhibition of extinction of the pole-jumping performance. In other experiments, the repeated administration of DHEC was followed by a decrease in the excessive grooming in aged rats, which is considered a sign of the lack of adaptability of these animals. A facilitation of the compensatory mechanisms in experimental models of vertigo has also been found in animals treated with DHEC.
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PMID:[Cerebral actions of dihydroergocristine]. 149 58

Aim of the study was to assess the activity of dihydroergocristine (DHEC, CAS 17479-19-5) in aged patients with impaired cognitive function. Twenty-five university hospital centres and 250 physicians participated in the study. 2,600 patients (1,104 males and 1,496 females, age range 50-80 years) were admitted to the study. Each patient was administered 6 mg/d DHEC for 120 days. Clinical evaluation was made through the SCAG Rating Scale registered at basal time, after 60 and 120 days. Responsivity to treatment was considered high when the final score was reduced by 30% and none if less than 10%. Analysis of results demonstrated that at the end of the study responsivity was high in 73% of cases, moderate in 20.4% and absent in 6.5%. Tolerability was very good as side effects were reported only in 3.16% of patients. Most frequent side effects were: nausea (1.23%), gastralgia (1.11%), headache (0.29%), hypotension (0.12%), vertigo (0.12%) and rash (0.08%). Drop-outs for gastralgia were reported only in 0.53% of the patients.
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PMID:[Epidemiologic study on the effectiveness and safety of dihydroergocristine in impaired memory and behavioral functions in aged humans]. 149 66

Ten multimorbid, geriatric, hospitalised patients, mean age 76 years, were treated for vertigo and received 10 mg flunarizine (CAS 52468-60-7; Sibelium) daily for 3 weeks. The study of the pharmacokinetics and pharmacodynamics of this dosage scheme revealed that the kinetics did not change during the three weeks of therapy. The terminal half-life is 7.3 +/- 3.3 days. Since a steady state concentration is only to be expected after about 5 half-lives, this condition was not fully met yet in most patients after three weeks. The data obtained from the patients examined are essentially identical with those in young and old healthy subjects. The unchanged kinetics during long-term treatment prevent side-effects due to cumulation on the one hand or the decrease of plasma levels to inactive concentrations resulting from enzyme induction. There was not measurable anti-aggregator effect on thrombocytes or erythrocytes. The effectiveness in connection with vertigo seems to be due to a direct labyrinth depressor activity and/or to a selective vasospecific action. No side-effects were observed during the three weeks of therapy.
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PMID:[Pharmacokinetics and pharmacodynamics of flunarizine in multimorbid, geriatric patients with vertigo]. 204 70

As has been demonstrated in binding studies the two opioids tilidine (CAS 27107-79-7)/naloxone (CAS 357-08-4) and tramadol (CAS 36282-47-0) differ in regard to their affinities to the opioid receptor site. Therefore it is of interest to evaluate whether such a difference in opioid affinity is also seen in the pharmacological effects of clinically relevant doses in man. Following institutional approval by the local ethical committee and informed consent, 12 volunteers received oral doses of tramadol (100 mg), tilidine/naloxone (100 mg) and placebo, respectively, in a randomized, double-blind cross-over design. In order to determine the degree of constipation, oral-caecal transit time was measured using the H2-exhalation test. Additionally, in order to evaluate a centrally mediated effect, the response of the pupil to light was quantified using the pupillary light reflex technique. Both, peripheral and central mediated effects were compared to placebo. Tramadol as well as tilidine/naloxone induced a significant (p < 0.05) prolongation of oral-caecal transit when compared to placebo. However, prolongation of oral-caecal transit was significantly longer in the tilidine/naloxone (p < 0.05) than in the tramadol group. Compared to tramadol, the pronounced constipating effect of tilidine/naloxone is likely to be due to the 10 fold higher affinity of that drug to the peripheral opioid receptor sites in the intestinal tract, which are responsible for normal propulsion. Such difference in binding is underlined by a central effect, the pupillary light reflex response. The amount of constriction of the iris to light was reduced after both opioids. Again, tilidine/naloxone significantly reduced (p < 0.001) the pupillary light reflex when compared to tramadol. Other side effects such as tiredness, nausea, emesis and dry mouth were more often reported after tilidine/naloxone than after tramadol (40% versus 15%; p < 0.05). Vertigo and perspiration were more often reported after tramadol than after after tilidine/naloxone (58% and 78% versus 8%; p < 0.01). All these data support the findings that while tramadol is considered an opioid, it does not mediate its main clinical relevant properties via binding at the opioid receptor. More likely, due to its monoaminergic reuptake mechanism, to a lesser extent opioid-like effects are induced.
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PMID:Effects of tramadol and tilidine/naloxone on oral-caecal transit and pupillary light reflex. 1068 12

Dihydroergotoxine mesylate (DHETM, CAS 8067-24-1), the combination of the mesylates of four dihydrogenated ergot alkaloid derivatives (dihydroergocornine, dihydroergocristine, alpha-dihydroergocryptine and beta-dihydroergocryptine), is used mainly for age-related cognitive impairment. The bioavailability of DHETM was investigated in a cross-over study on 20 male healthy volunteers to whom two single doses of 9 mg DHETM were administered either in tablets (Orphol spezial) or in oral solution (Orphol forte). DHETM was assayed in serum with a double radioimmunoassay method displaying a satisfactory cross-reactivity with the principal components of DHETM. After administration of tablets the peak of DHETM was (mean +/- SE) 124 +/- 16 pg/ml, the tmax 1.15 +/- 0.21 h, the AUC 790 +/- 93 pg/ml x h and the terminal elimination half-life 7.54 +/- 1.23 h. After oral solution the peak of DHETM was 176 +/- 16 pg/ml, the tmax 0.50 +/- 0.04 h, the AUC 779 +/- 94 pg/ml x h and the terminal elimination half-life 6.13 +/- 0.76 h. The bioavailability of DHETM from tablets vs. that from oral solution differed only by a retard related to the dissolution time of DHETM from the tablets, but not for other pharmacokinetic parameters. The relatively high two single doses of 9 mg DHETM administered to the 20 subjects were well tolerated, causing only known and expected adverse reactions to DHETM (tiredness, headache and vertigo) that did not require discontinuation of the study.
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PMID:Bioavailability and pharmacokinetic profile of dihydroergotoxine from a tablet and from an oral solution formulation. 1121 21

It is well accepted that long-term administration of opioids results in a dose-related constipation. No data so far have demonstrated conclusively whether such constipation is also seen after intake of a controlled release formulation. It was therefore of interest to evaluate whether increasing doses of a controlled release formulation of dihydrocodeine (DHC, CAS 125-28-0) after oral administration also induces a dose-related increase in constipation. Additionally, it was of interest to study whether such a peripheral opioid-related side effect is also seen in another, central receptor-mediated effect, the constriction of the pupil, at clinically relevant doses. Twelve volunteers were given controlled release DHC (60 and 120 mg, respectively) or placebo orally within a randomized, double-blind cross-over study. In order to determine the degree of constipation, oro-cecal transit time was measured using the H2-exhalation test. Additionally, in order to evaluate a centrally mediated effect, the response of the pupil to light was quantified using the pupillary light reflex technique. Both, peripherally and centrally mediated effects were compared to placebo. DHC at both dosages induced a significant (p < 0.01) prolongation of oro-cecal transit time when compared to placebo. However, prolongation of oro-cecal transit was not significantly longer when comparing the lower (60 mg) with the higher dose (120 mg). DHC also induced a significant (p < 0.005) depression of the pupillary light reflex from 53.9 mm (control) to 8.3 and 7.4 mm, respectively. Similar to intestinal transit, the pupillary light reflex was not significantly different among the two doses of DHC. Also, both dosages induced a similar amount of side effects. Tiredness and dry mouth were reported in 80% after both doses while vertigo was reported in 5% and 1% complained of headache. None of the volunteers reported nausea or emesis. It is concluded that opioid receptor sites, which are located in the plexus myentericus of the intestinal wall, are responsible for the delay in propulsion. Because of the controlled release of a fixed amount of DHC over time there is constant binding of the ligand followed by a constant conformational change of peripheral and central receptor sites. Thus constant release induces no dose-related increase in oro-cecal transit and inhibition of the pupillary light reflex.
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PMID:Dose-related effects of controlled release dihydrocodeine on oro-cecal transit and pupillary light reflex. A study in human volunteers. 1121 27

It is known that sedation by H1 antihistaminic drugs can be reduced or avoided if slow release formulations are used for their administration, probably because of a slower increase of the drug concentration in plasma and brain. The aim of this study was to compare two different formulations of dimenhydrinate (CAS 523-87-5), a single fast release tablet with three chewing gums (divided dose principle), with regard to their efficacy in a motion sickness model and their detrimental effect on vigilance and central nervous system (CNS) performance. Caloric stimulation of the eardrum (air at 44 degrees C) was used to induce the symptoms of motion sickness in 24 symptomatic volunteers in a three-way cross-over design comparing three chewing gums (Superpep forte, chewed for 30 min each) containing 20 mg dimenthydrinate each with a 50 mg dimenhydrinate tablet and placebo. During caloric stimulation the following parameters were measured in order to compare efficacy: Quantitative analysis of sodium excretion by sweat (main target parameter), subjective well being (vertigo) by visual analogue scales (VAS) and frequency of binocular nystagmus by computer nystagmography. Unwanted effects on vigilance and CNS performance were measured by means of the N1-P2 peak to peak amplitudes of auditory evoked potentials (AEPs) as an objective, quantitative parameter of vigilance and the latency to correct responses and the number of correct responses (complex choice reaction task) in the oculodynamic test (ODT) as parameters of complex choice reaction ability. As a main efficacy result sodium excretion by sweat was markedly reduced by the chewing gums and by the tablet. The differences to placebo were highly significant (chewing gums vs. placebo p < 0.0001, tablet vs. placebo p < 0.0001). There was no relevant and no significant difference between both medications (p = 0.308). The secondary efficacy parameters, frequency of binocular nystagm and the VAS vertigo were markedly reduced by both medications in comparison to placebo, i.e. both medications were markedly effective. In both cases, however, this result failed statistical significance. The unwanted depressing effects on vigilance and CNS performance of the chewing gums were less pronounced than that of tablets. The N1/P2 peak-to-peak amplitudes of the AEPs were significantly reduced by both the chewing gums and the tablets. The effect of the tablets was, however, larger than that of the chewing gums. This highly significant (tablet vs. chewing gums, p = 0.0003) difference shows that the tablet had a larger depressing effect on vigilance (greater sedation). In line with this result, the number of correct responses in the ODT was markedly and significantly reduced by the tablet (p = 0.0027) but not significantly by the chewing gums (p = 0.8140). The difference between the tablet and the chewing gums was highly significant (p = 0.0052). The complex choice reaction time was markedly and nearly significantly (p = 0.0558) prolonged by the tablet whereas the chewing gums produced only a very small and insignificant prolongation. That the objective measurements of vigilance and CNS performance showed significantly larger detrimental effects of the tablet than of the chewing gums is probably a consequence of a faster increase of the dimenhydrinate concentration in the CNS after administration of the tablet in comparison to the divided dose principle of the chewing gums.
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PMID:A randomised, placebo-controlled study comparing two formulations of dimenhydrinate with respect to efficacy in motion sickness and sedation. 1218 76