Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Depression is a common comorbidity in patients with heart failure or implantable cardioverter-defibrillators (ICDs). A 35-year-old woman with depression, nonischemic cardiomyopathy, and a history of cardiac arrest had an ICD implanted. During initial testing, the device failed to internally defibrillate the patient. Venlafaxine, an antidepressant with cardiac sodium channel blocking activity, was identified as a potential contributor to her elevated defibrillation threshold. After the venlafaxine was discontinued, the ICD was able to successfully internally defibrillate the patient. Clinicians should be aware of this potential adverse drug-device interaction. Further studies are needed to determine the clinical significance of venlafaxine therapy in patients with ICDs.
 ...
PMID:Elevated defibrillation threshold with venlafaxine therapy. 1533 58

A 75-year-old man suffered sustained ventricular tachycardia with syncopal attack. Ventricular tachycardias appeared repeatedly, and an electrical defibrillator was used after an anti-arrhythmic drug, such as lidocaine or mexiletine, proved ineffective. The tachycardias had multiple origins, and the signal-averaged electrocardiogram (SAECG) showed ventricular late potential before the administration of amiodarone. After administration, the filtered QRS and duration of the late potential increased, but the recurrence of tachycardias was suppressed. The reason for this is thought to be that amiodarone blocked the sodium channel and delayed conduction, consequently blocking reentry, because amiodaron has antiarrhymic properties with a prolongation of refractoriness and minimal effect on conduction velocity in ventricular myocardium, and inhibits sympathetic activity, and blocks L-type calcium channel besides the depression of the fast sodium channel. In this case, SAECG predicted to some degree whether or not this patient's ventricular tachycardia would respond to amiodarone.
 ...
PMID:A patient with sustained ventricular tachycardia: identification of a responder to amiodarone using signal-averaged electrocardiogram. 1546 Sep 15

Phenytoin, a classical anticonvulsant has been little studied in bipolar disorder. We completed a trial of phenytoin in mania and schizoaffective disorder, manic type. Thirty-nine patients entered a 5-wk double-blind controlled trial of haloperidol+phenytoin vs. haloperidol+placebo; 30 patients completed at least 3 wk; 25 completed 5 wk. Significantly more improvement was observed in those patients receiving phenytoin. Phenytoin has not previously been studied prophylactically in bipolar patients. Bipolar patients were studied who had at least one episode per year in the previous 2 yr despite ongoing prophylaxis. Patients were stable for a mean of 4 months (range 1-13) before entering the study. Phenytoin or placebo was added to their current therapy in a double-blind cross-over design for 6 months in each phase. Thirty observation periods of 6 months each were studied for 23 patients. Three patients had relapse on phenytoin and nine had relapse on placebo. There was a significant prophylactic effect of phenytoin in bipolar disorder [Cox's F test for comparing survival in two groups: F(6, 18)=3.44, p=0.02]. This study suggests prophylactic effects of add-on phenytoin in bipolar illness. However, the number of patients was small and confirmation is necessary. Lamotrigine has recently been reported to have antidepressant effects. In the past, small studies showed antidepressant effects for carbamazepine and valproate. To determine if such effects could be a class property of other voltage-activated sodium channel blockers such as phenytoin, we performed a double-blind controlled trial of phenytoin vs. fluoxetine in unipolar depression. Thirty-three depressed patients entered the study, and 28 completed at least 3 weeks and were included in data analyses. Weekly Hamilton Depression Scales for 6 wk showed no difference between fluoxetine and phenytoin. Clearly pharmaceutical company funding for clinical trials or advertising for phenytoin is minimal and this must be taken into account in evaluating literature on phenytoin vs. other drugs. The present data suggests that effects on affective disorder may be common to many anticonvulsants.
 ...
PMID:Phenytoin: an anti-bipolar anticonvulsant? 1642 79

Migraine is the most frequent primary headache disorder. It is a neurovascular disorder in which the primary abnormality is thought to be a neuronal excitability underlined by a complex genetic susceptibility. Epidemiogenetic studies have shown that migraine without aura and migraine with aura are polygenic conditions. The three known migraine genes have been identified by the study of the unique monogenic variety of migraine, i.e. familial hemiplegic migraine. These genes all encode ion transporters: the P/Q type calcium channel, a calcium/potassium ATPase and a sodium channel. According to the latter hypothesis about the mechanisms of migraine attacks, poorly known triggers initiate a cortical wave of depolarisation that is responsible for the transient aura symptoms. This cortical spreading depression induces several biochemical changes which, by diffusion through the extracellular space, stimulate the trigeminovascular fibres. These fibres release vasoactive neuropeptides that initiate the neurogenic inflammation. Trigeminovascular fibres transmit nociceptive information centrally via the brainstem. The trigeminovascular fibres also activate the parasympathetic system that is responsible for the persistence of vasodilation in meningeal vessels.
 ...
PMID:[Mechanisms and genetics of migraine]. 1684 22

The seas and oceans around Australia harbour numerous venomous jellyfish. Chironex fleckeri, the box jellyfish, is the most lethal causing rapid cardiorespiratory depression and although its venom has been characterised, its toxins remain to be identified. A moderately effective antivenom exists which is also partially effective against another chirodropid, Chiropsalmus sp. Numerous carybdeids, some unidentified, cause less severe illness, including Carybdea rastoni whose toxins CrTX-A and CrTX-B are large proteins. Carukia barnesi, another small carybdeid is one cause of the 'Irukandji' syndrome which includes delayed pain from severe muscle cramping, vomiting, anxiety, restlessness, sweating and prostration, and occasionally severe hypertension and acute cardiac failure. The syndrome is in part caused by release of catecholamines but the cause of heart failure is undefined. The venom contains a sodium channel modulator. Two species of Physalia are present and although one is potentially lethal, has not caused death in Australian waters. Other significant genera of jellyfish include Tamoya, Pelagia, Cyanea, Aurelia and Chyrosaora.
 ...
PMID:Australian venomous jellyfish, envenomation syndromes, toxins and therapy. 1692 89

Bepridil is an investigational calcium antagonist that also has fast sodium channel blocking and antidysrhythmic properties. In the present study, the potential interactions of bepridil with volatile anesthetics on cardiac electrophysiologic parameters were evaluated in open-chest dogs. Twenty-four dogs anesthetized with enflurane (n=6), halothane (n=6), isoflurane (n=6), or chloralose (n=6) received 2.5 mg/kg of bepridil intravenously (IV). Twenty-five additional dogs anesthetized with enflurane (n=7), halothane (n=6), isoflurane (n=6), or chloralose (n=6), received bepridil, 5.0 mg/kg, IV. Dogs anesthetized with cloralose served as controls. Cardiac electrophysiologic parameters were measured after the dogs were anesthetized and were repeated 5, 15, 30, 45, and 60 minutes after bepridil infusion. Plasma bepridil concentrations were also determined at the above time points. Synergy between bepridil and enflurane was demonstrated in the following cardiac electrophysiologic parameters: depression of sinus node function as evidenced by severe depression of sinus node automaticity and conduction; depression of atrioventricular function as evidenced by prolongation of the atrial-His bundle interval and the Wenckebach R-R interval; and, prolongation of the atrial effective refractory period. No synergy was demonstrated between bepridil and halothane or isoflurane when compared to bepridil's effects during chloralose anesthesia. It is concluded that significant synergistic cardiac electrophysiologic effects exist between bepridil and enflurane in dogs. It is recommended that caution be used when anesthetizing patients receiving bepridil with enflurane until human data on the use of this combination of pharmacologic agents is available.
 ...
PMID:Cardiac electrophysiologic interactions of bepridil, a new calcium antagonist, with enflurane, halothane, and isoflurane. 1717 71

We previously showed in dissociated cultures of fetal rat spinal cord that disinhibition-induced bursting is based on intrinsic spiking, network recruitment, and a network refractory period after the bursts. A persistent sodium current (I(NaP)) underlies intrinsic spiking, which, by recurrent excitation, generates the bursting activity. Although full blockade of I(NaP) with riluzole disrupts such bursting, the present study shows that partial blockade of I(NaP) with low doses of riluzole maintains bursting activity with unchanged burst rate and burst duration. More important, low doses of riluzole turned bursts composed of persistent activity into bursts composed of oscillatory activity at around 5 Hz. In a search for the mechanisms underlying the generation of such intraburst oscillations, we found that activity-dependent synaptic depression was not changed with low doses of riluzole. On the other hand, low doses of riluzole strongly increased spike-frequency adaptation and led to early depolarization block when bursts were simulated by injecting long current pulses into single neurons in the absence of fast synaptic transmission. Phenytoin is another I(NaP) blocker. When applied in doses that reduced intrinsic activity by 80-90%, as did low doses of riluzole, it had no effect either on spike-frequency adaptation or on depolarization block. Nor did phenytoin induce intraburst oscillations after disinhibition. A theoretical model incorporating a depolarization block mechanism could reproduce the generation of intraburst oscillations at the network level. From these findings we conclude that riluzole-induced intraburst oscillations are a network-driven phenomenon whose major accommodation mechanism is depolarization block arising from strong sodium channel inactivation.
 ...
PMID:Riluzole-induced oscillations in spinal networks. 1734 72

A number of putative endocannabinoids were found to modify the binding of [(3)H]batrachotoxinin A-20alpha-benzoate ([(3)H]BTX-B) to site 2 on voltage-gated sodium channels of mouse brain and achieve functional inhibition of sodium channels in vitro. 2-Arachidonoyl-glycerol (2-AG), arachidonoyl glycerol ether (AGE), N-arachidonoyl-dopamine (NADA) gave almost complete inhibition of [(3)H]BTX-B binding with IC(50) values of 90.4, 51.2 and 20.7 microM, respectively. The CB1 receptor antagonist AM251 (2 microM) had no effect on the displacement of radioligand by these endocanabinoids. Arachidonoyl-glycine (A-Gly) and arachidonoyl-GABA (A-GABA) were apparently less effective inhibitors of [(3)H]BTX-B binding giving 14.8+/-2.2 and 23.9+/-4.8% inhibition at 100 microM. Phenylmethanesulphonylfluoride (PMSF) did not alter the inhibitory effects of 2-AG, AGE, NADA and A-Gly on binding, but the efficacy of 100 microM A-GABA was increased by 60.3+/-6.3% (P<0.05). Scatchard analyses showed that 2-AG, AGE and NADA reduce the binding of [(3)H]BTX-B by lowering B(max) although increases in K(D) were also evident for AGE and NADA. Our kinetic experiments found that 2-AG, AGE and NADA increase the dissociation velocity of radioligand from site 2 on sodium channels demonstrating that these endocannabinoids operate as allosteric inhibitors of [(3)H]BTX-B binding. 2-AG, AGE and NADA inhibited veratridine-dependent (TTX-suppressible) depolarization of the plasma membrane of synaptoneurosomes at low micromolar concentrations and again the capacities of A-Gly and A-GABA to inhibit this response were less pronounced. The three most effective endocannabinoids (2-AG, AGE and NADA) were then examined in a synaptosomal transmitter release assay where they were observed to inhibit sodium channel- (veratridine-dependent) release of l-glutamate and GABA in the low micromolar range. These effects also occurred through a mechanism that was not influenced by 2 microM AM251. It is concluded that direct inhibition of sodium channel function leading to reduced neuronal excitation and depression of presynaptic release of amino acid transmitters is a property shared by several endocannabinoids.
 ...
PMID:Inhibition of [3H]batrachotoxinin A-20alpha-benzoate binding to sodium channels and sodium channel function by endocannabinoids. 1788 43

There is increasing evidence that the late sodium current of the sodium channel in myocytes plays a critical role in the pathophysiology of myocardial ischemia and thus is a potential therapeutic target in patients with ischemic heart disease. Ranolazine, an inhibitor of the late sodium current, reduces the frequency and severity of anginal attacks and ST-segment depression in humans, and unlike other antianginal drugs, ranolazine does not alter heart rate or blood pressure. In experimental animal models, ranolazine has been shown to reduce myocardial infarct size and to improve left ventricular function after acute ischemia and chronic heart failure. This article reviews published data describing the role of late sodium current and its inhibition by ranolazine in clinical and experimental studies of myocardial ischemia.
 ...
PMID:Late sodium current inhibition as a new cardioprotective approach. 1846 46

As it is well known opioids are the most powerful drugs used for acute and chronic pain, although, their several serious side effects, such as respiratory depression, mental clouding, constipation, and tolerance dependence producing capacity, as well as large interpatient variability in responses limit their safe everyday use. Furthermore, the treatment of certain types of pain (e.g. neuropathic pain) is not very satisfactorily managed. Consequently, there is a continuous need to find analgesics efficient against chronic neuropathic pain and avoid these side actions and still retain opioid like potency. There are several possible way to find new targets for these purposes. Recently opioid receptors have been identified on peripheral processes of sensory neurons. These findings provide new insights into intrinsic mechanisms of pain control and suggest innovative strategies for developing drugs and alternative approaches to pain treatment. In the effort to discover better analgesic drugs for chronic pain, attention is being paid to specific ion channels at the periphery, include members of transient receptor potential family (TRPV1, capsaicin receptors), as well as P2x receptors, sensitive to purines released from tissue injury. A special tetradotoxin-resistant, voltage dependent type of sodium channel is associated with dorsal root ganglia neurons is blocked by mexiletine, used in chronic pain. A synthetic peptide analogue of marine snail toxin ziconitine blocks N-type calcium channels. GABA and NMDA receptors are also involved in the antinociceptive actions of gabapentin and ketamine, respectively. Furthermore nicotine and analogues (epibatidine) induce analgesia through nicotinic ACh receptors. We studied mostly the peripheral targets of hydrophilic heterocyclic opioids in antinociceptive processes.
 ...
PMID:[Central and peripheral mechanisms in antinociception: current and future perspectives]. 1895 16


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>