Mechanism of action of alpha2delta ligands: voltage sensitive calcium channel (VSCC) modulators.

Voltage sensitive calcium channels (VSCCs) have unique structures and functions that distinguish them from other ion channels, especially the voltage sensitive sodium channels (VSSCs). Modulation of VSCCs by certain drugs such as pregabalin and gabapentin via binding to the alpha2delta subunits of VSCCs can lead to anticonvulsant, anxiolytic, and chronic pain-relieving actions.

Anticonvulsants as mood stabilizers and adjuncts to antipsychotics: valproate, lamotrigine, carbamazepine, and oxcarbazepine and actions at voltage-gated sodium channels.

Actions of certain anticonvulsants upon voltage-gated sodium channels may not only explain why they are effective mood stabilizers but may also explain why they could be useful adjuncts to antipsychotics for resistant psychosis.

Anticonvulsants and the relief of chronic pain: pregabalin and gabapentin as alpha(2)delta ligands at voltage-gated calcium channels.

Anticonvulsants that act as ligands at alpha(2)delta subunits of voltage-gated calcium channels are proving to be novel treatments for chronic pain.

Examination of nighttime sleep-related problems during double-blind, placebo-controlled trials of galantamine in patients with Alzheimer's disease.

Background: Acetylcholinesterase inhibitors (AChEI) are now widely used as treatment for Alzheimer's disease (AD). Their cholinomimetic action has the potential to influence sleep quality and donepezil has been associated with sleeprelated adverse events. This study examined whether galantamine, an AChEI with nicotinic modulation, is associated with nighttime sleeprelated problems.

Psychopharmacology of anticonvulsants: do all anticonvulsants have the same mechanism of action?

Anticonvulsants are not a single therapeutic class, but are composed of multiple distinct subclasses with different mechanisms of action, efficacies, and side effects.

A critical review of atypical antipsychotic utilization: comparing monotherapy with polypharmacy and augmentation.

The atypical antipsychotics risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole have become first-line treatment for schizophrenia because they reduce the positive symptoms of psychosis but do not have a high incidence of extrapyramidal symptoms. However, these agents, like other antipsychotics, may take as long as 16 or more weeks to produce a response, and even with prolonged treatment are unlikely to evoke responses greater than 50% improvement in symptoms. This has led to the experimental use of high atypical antipsychotic doses, antipsychotic polypharmacy, and augmentation with other psychotropic drugs, all of which occur commonly in clinical practice.

Symptoms and circuits, part 3: schizophrenia.

Schizophrenia is composed of not only positive symptoms, but also cognitive and affective symptoms that contribute significantly to morbidity. Each of these symptoms may be mediated by a separate and distinct neuronal circuit.

Brainstorms: symptoms and circuits, part 2: anxiety disorders.

Numerous anxiety disorders may have malfunctioning neuronal circuits in common, which may account for the overlapping symptoms and frequent comorbidity of many anxiety disorders with one another.

Selectivity of SSRIs: individualising patient care through rational treatment choices.

Despite a common mode of action [inhibition of the 5-hydroxytryptamine (5-HT) neuronal reuptake transporter], proven antidepressant efficacy and a similar range of indications (depression and a variety of anxiety disorders), the unique secondary binding properties of each selective serotonin reuptake inhibitor (SSRI) account for clinically significant differences in tolerability and side-effect profiles, particularly in some patients. Secondary properties within the class of SSRIs include some combination of actions at noradrenergic, dopaminergic, muscarinic cholinergic, histaminergic and sigma receptors. In addition, most SSRIs inhibit at least one of the cytochrome P450 enzymes, resulting in potential pharmacokinetic interactions with co-prescribed drugs.

Escitalopram in the treatment of panic disorder: a randomized, double-blind, placebo-controlled trial.

Background: Escitalopram, the therapeutically active isomer of the racemic selective serotonin reuptake inhibitor antidepressant citalopram, has shown significant anxiolytic effects in placebo-controlled clinical trials of social anxiety disorder, generalized anxiety disorder, and anxiety symptoms associated with major depression. This study evaluated the safety and efficacy of escitalopram in outpatients diagnosed with panic disorder.

Method: Male and female outpatients between 18 and 80 years of age meeting DSM-IV criteria for panic disorder, with or without agoraphobia, were randomly assigned to 10 weeks of double-blind treatment with escitalopram, citalopram, or placebo in a study conducted from September 1999 to July 2001.

Symptoms and circuits, part 1: major depressive disorder.

Major depressive disorder comprises multiple symptoms. Each symptom may be mediated by separate and distinct neuronal circuits.

Brain circuits determine destiny in depression: a novel approach to the psychopharmacology of wakefulness, fatigue, and executive dysfunction in major depressive disorder.

Recent advances in neuropharmacology and neuroimaging are mapping the topography of symptoms in major depressive disorder (MDD). Different malfunctioning neuronal circuits apparently mediate different symptoms in MDD. Since all patients with MDD do not have the same symptoms, this implies that they may not all have the same malfunctioning circuits.

Differences in mechanism of action between current and future antidepressants.

Antidepressants are divided into several classes on the basis of their pharmacologic mechanisms of action, which are thought to be responsible for both their therapeutic actions and their side effect profiles. All classes currently available in the United States affect serotonin, norepinephrine, and/or dopamine neurotransmission. New agents in development also affect neurotransmission of such monoamines and include serotonin-norepinephrine reuptake inhibitors, serotonin-selective agents, selective monoamine oxidase inhibitors, and selective norepinephrine reuptake inhibitors.

Antidepressants and somatic symptoms: therapeutic actions are expanding beyond affective spectrum disorders to functional somatic syndromes.

Having expanded their original role as primary treatment for depression to preferred treatment for anxiety disorders, antidepressants are now emerging as potential therapeutic agents for many other disorders characterized by distressing or even painful somatic symptoms.

The ups and downs of novel antiemetic drugs, part 2: an illustration.

Novel antiemetic drugs block either neurokinin-1 receptors or serotonin-3 receptors. Research into the neuropharmacology of vomiting is providing insight into the ways substance P and serotonin interact within the central nervous system that could lead to additional applications of neurokinin-1 antagonists for the treatment of depression and stress.

The ups and downs of novel antiemetic drugs, part 1: substance P, 5-HT, and the neuropharmacology of vomiting.

Novel antiemetic agents such as the newly approved aprepitant (Emend) target receptors for substance P, known as neurokinin-1 (NK(1)) receptors. When NK(1) receptors are blocked in the vomiting center of the brainstem, chemotherapy-induced emesis is reduced. It is possible that blocking NK(1) receptors elsewhere in the CNS will lead to therapeutic actions in depression and other stress-related disorders.

Neurotransmission of cognition, part 3. Mechanism of action of selective NRIs: both dopamine and norepinephrine increase in prefrontal cortex.

Selective norepinephrine reuptake inhibitors exploit the fact that dopamine transporters are absent in prefrontal cortex, so dopamine has to hitchhike a ride on the norepinephrine transporter in order to be inactivated. Thus, blocking norepinephrine transporters leads to an increase in both dopamine and norepinephrine levels in prefrontal cortex as well as improvement in cognition in attention-deficit/hyperactivity disorder.