Disease relevance of cyclandelate

• These results suggest that cyclandelate may be a useful alternative in migraine prophylaxis [1].
• Cyclandelate in the treatment of vertigo of circulatory origin. A study in general practice [2].
• Perceived efficacy of cyclandelate in the treatment of cochleovestibular and retinal disturbances related to cerebrovascular insufficiency. A study in general practice comprising 2772 patients [3].
• Thus, cyclandelate may exert its clinical activity in cerebral ischaemia or hypoxia at least in part through a calcium modulatory effect [4].
• Previous trials have demonstrated a clinical and electrophysiological improvement of diabetic peripheral polyneuropathy in diabetic patients treated with cyclandelate at a dosage of 1600 mg/day [5].

Psychiatry related information on cyclandelate

• Effect of cyclandelate on dementia [6].
• Six psychological tests, which reflect various aspects of higher cortical ability, were used to evaluate the effect of cyclandelate on the dementia [6].
• Thus, our results indicate that this drug may be therapeutically useful in memory disorders of various aetiology, and that further exploration of the place of cyclandelate in this clinical area is needed [7].
• Cyclandelate in the treatment of multi-infarct dementia. Interim findings from a multicentre study in general practice [8].
• At 90 days, significant improvements were observed in patients given cyclandelate in measurements of P100 latency in the left eye, neurological impairment, dementia scores, ischaemia scores, Gottfries mental deterioration scale, Hamilton depression scores, short term visual memory, long term memory, Bender-Gestalt test and Koh's blocks test [9].

High impact information on cyclandelate

• Effect of food on the bioavailability of cyclandelate from commercial capsules [10].
• In a double-blind, parallel-group randomised trial of 3 months' duration, the efficacy of cyclandelate 800 mg twice daily in migraine prophylaxis was compared with that of flunarizine 5mg daily in 40 patients [1].
• To investigate the perceived efficacy and safety of cyclandelate when used in general practice, an open multicentre study was performed comprising 2772 patients with symptoms of vertigo, tinnitus or visual disturbances thought to result from cerebrovascular insufficiency [3].
• It is likely that the inhibition by cyclandelate of cholesterol esterification in whole cells is due to a direct inhibition of the hepatic microsomal enzyme acyl coenzyme A: cholesterol acyl transferase (ACAT), since addition of the drug in a concentration of 100 mumol/L inhibited by 74% the activity of ACAT derived from rat liver [11].
• This inhibition was dose dependent and optimal at about 50 mumol/L, the concentration at which Ca++ mobilisation was suppressed to about 10% of control values, and at which cyclandelate inhibits platelet aggregation [12].

Chemical compound and disease context of cyclandelate

• Comparative efficacy of cyclandelate versus flunarizine in the prophylactic treatment of migraine [1].
• The percentage of patients with a reduction in migraine attacks of > or = 50% treated with cyclandelate (37.0%) or propranolol (42.3%) was not significantly superior to placebo (30.9%; p > 0.025) [13].
• New drugs in migraine prophylaxis include cyclandelate, valproic acid and magnesium [14].
• In hypercapnia, a more pronounced increase in LCBF than in normocapnia was seen with CY, HE, NAF, and VI and a decrease or lesser effect with HA, IF, VC and XN [15].

Biological context of cyclandelate

• Moreover, in the presence of cyclandelate (100 mumol/L), cholesterol esterification was inhibited by 90% in fibroblasts cultured with LDL and in human monocyte derived macrophages cultured with acetyl-LDL [11].
• Further exposure of fibroblasts to cyclandelate for 17 hours resulted in a similar inhibition in the uptake and hydrolysis of LDL [11].
• The results of these experiments appeared to indicate that cyclandelate, cyclandelate alcohol and flunarizine were approximately equipotent in maintaining RBC filtration and blood viscosity values [16].
• Hence, this study investigated the interaction of cyclandelate, cyclandelate alcohol and cyclandelate acid with the binding sites for radioactively labelled 3H-nitrendipine, a Ca++ entry blocker of the 1,4-dihydropyridine type, on rat cerebral cortex membranes [4].
• In vivo inhibition of hepatic lipogenesis in the rat by cyclandelate (3,3',5-trimethylcyclohexanylmandelate) [17].

Anatomical context of cyclandelate

• Cyclandelate as a calcium modulating agent in rat cerebral cortex [4].
• Influence of cyclandelate on in vitro red blood cell deformability [16].
• Therefore, the effects of cyclandelate on prostacyclin (PGI2) release and cytosolic free calcium were investigated in cultured human endothelial cells [18].
• The results strengthen the hypothesis that cyclandelate maintains red cell deformability by inhibiting calcium entry through the red cell membrane [16].
• The hypothesis that the calcium modulating property of cyclandelate is responsible for the inhibition of blood platelet functions is strengthened by the inability of the drug to inhibit the calcium-independent platelet aggregation induced by ristocetin [19].

Associations of cyclandelate with other chemical compounds

• Cyclandelate and cyclandelate alcohol, but not cyclandelate acid, in a dose-dependent fashion prevented platelet aggregation and the concomitant 14C-serotonin release and TxB2 formation induced by adenosine diphosphate, platelet activating factor and collagen [19].
• To test this hypothesis, a double-blind multicentre study was performed in 214 patients to investigate the efficacy and tolerability of cyclandelate compared to placebo and propranolol [13].
• A method was developed for the simultaneous determination of cyclandelate and mandelic acid concentrations in plasma, involving extraction from plasma followed by trimethylsilylation and chromatography of the derivatives on a glass capillary column with hydrogen flame-ionization detection [20].
• Rat hepatocytes also accumulated cyclandelate rapidly, hydrolysing the ester and excreting trimethylcyclohexanol into the medium [21].
• Blood specimens were collected at 1-6 h after oral administration of 1600 mg cyclandelate, and the ester and acid were extracted from plasma in acid medium using n-hexane/isopropyl alcohol [22].

Gene context of cyclandelate

• The inhibition of cholesterol esterification by cyclandelate in transformed mouse macrophages [23].
• The effects of two acylcoenzyme A: cholesterol acyltransferase (ACAT) inhibitors, cyclandelate and a non-hydrolysable ether analogue, benzyl3,3,5-trimethylcyclohexanol on low density lipoprotein metabolism in macrophages and hepatocytes [24].
• Cyclandelate bound to beta 2-sites and blocked calcium accumulation [25].
• Of particular interest is that following cyclandelate treatment the absolute theta power remained almost unchanged and an increase of P300 amplitude was observed [26].
• An average reduction of about 50% in FA, TPI and AwH was already observed in the cyclandelate group after 4-6 weeks suggesting an early onset of action [27].

Analytical, diagnostic and therapeutic context of cyclandelate

• In a double-blind, cross-over study, patients received 200 mg of cyclandelate four times daily for six weeks and a placebo for six weeks [6].
• Twenty-one patients with cerebral arteriosclerosis were treated for twelve months with placebo or cyclandelate (Cyclospasmol), 400 mg four times daily, in a double-blind study with medication cross-over after six months [28].
• Simultaneous determination of cyclandelate and its metabolite in human plasma by capillary column gas-liquid chromatography [20].
• In the cyclandelate group a significant reduction of all CNV components was observed and the changes in amplitudes compared to baseline were more pronounced after treatment [29].
• The anti-hypoxaemic effect of cyclandelate in man measured in human volunteers using computer-assisted oculodynamic methodology [30].

References