This article discusses the mechanism of action of Wellbutrin (bupropion) and relates the drug's neuropharmacologic effects to its clinical efficacy and side effect profiles. The preclinical and clinical data show that bupropion acts via dual inhibition of norepinephrine and dopamine reuptake and is devoid of clinically significant serotonergic effects or direct effects on postsynaptic receptors. With respect to treatment of depression, these catecholaminergic effects of bupropion tended to produce more robust effects on anhedonia/positive affect. Augmenting or switching antidepressants with bupropion has become an increasingly common strategy in the treatment of resistant depression. Bupropion has been suggested for the treatment of bipolar depression , because of its efficacy and a lower risk of inducing switches to hypomania or mania. Clinically, SR formulation, side effects are infrequent and benign, would be used without a risk of seizure in dose up to 400 mg/day.
Antidepressive Agents ; Bipolar Disorder ; Bupropion* ; Depression* ; Dopamine ; Neuropharmacology ; Norepinephrine ; Seizures

The use of pharmacological agents is often the preferred approach to the management of vestibular dysfunction. In the vestibular sensory pathways, the sensory neuroepithelia are thought to be influenced by a diverse number of neuroactive substances that may act to enhance or inhibit the effect of the primary neurotransmitters [i.e., glutamate (Glu) and acetylcholine (ACh)] or alter their patterns of release. This review summarizes various efforts to identify drug targets including neurotransmitter and neuromodulator receptors in the vestibular sensory pathways. Identifying these receptor targets provides a strategic basis to use specific pharmacological tools to modify receptor function in the treatment and management of debilitating balance disorders. A review of the literature reveals that most investigations of the neuropharmacology of peripheral vestibular function have been performed using in vitro or ex vivo animal preparations rather than studying drug action on the normal intact vestibular system in situ. Such noninvasive approaches could aid the development of more accurate and effective intervention strategies for the treatment of dizziness and vertigo. The current review explores the major neuropharmacological targets for drug action in the vestibular system.
Acetylcholine ; Animals ; Dizziness ; Glutamic Acid ; In Vitro Techniques ; Neuropharmacology ; Neurotransmitter Agents ; Receptors, Neurotransmitter ; Vertigo

The use of pharmacological agents is often the preferred approach to the management of vestibular dysfunction. In the vestibular sensory pathways, the sensory neuroepithelia are thought to be influenced by a diverse number of neuroactive substances that may act to enhance or inhibit the effect of the primary neurotransmitters [i.e., glutamate (Glu) and acetylcholine (ACh)] or alter their patterns of release. This review summarizes various efforts to identify drug targets including neurotransmitter and neuromodulator receptors in the vestibular sensory pathways. Identifying these receptor targets provides a strategic basis to use specific pharmacological tools to modify receptor function in the treatment and management of debilitating balance disorders. A review of the literature reveals that most investigations of the neuropharmacology of peripheral vestibular function have been performed using in vitro or ex vivo animal preparations rather than studying drug action on the normal intact vestibular system in situ. Such noninvasive approaches could aid the development of more accurate and effective intervention strategies for the treatment of dizziness and vertigo. The current review explores the major neuropharmacological targets for drug action in the vestibular system.
Acetylcholine ; Animals ; Dizziness ; Glutamic Acid ; In Vitro Techniques ; Neuropharmacology ; Neurotransmitter Agents ; Receptors, Neurotransmitter ; Vertigo

A parallel distributed neural network model of basal ganglia based on the neuroanatomy, neuropharmacology and neurophysiology is described. Despite recent advances in the understanding of the pathophysiology of movement disorders, little is known about the precise function the banal ganglia play in the control of movement. This article reviews an approach to studying the function of neural systems that is based on the use of a class of a computer models as parallel distributed processors (PDPs) and indicate its potential range of applications to the study of movement disorders. On this model, nigro-striatal dopaminergic system is considered as a threshold on the cortico-striatal glutamatergic fibers. So this dopaminergic system can control the striatal output to the globus pallidus and the striatal net model is consistent with clinical effect of Parkinson's disease that shows loss of dopaminergic function on the striatal medium spiny neurons due to nigral degeneration. The pallidal net is more complicated due to the probable reciprocal effects of dopaminergic function on the direct and indirect pathways of striato-pallidal connections which is not well known at present. But the neural network modal of PDPs would be a important field of neuroscience in a near future.
Basal Ganglia* ; Computer Simulation ; Ganglia ; Globus Pallidus ; Movement Disorders ; Neural Networks (Computer)* ; Neuroanatomy ; Neurons ; Neuropharmacology ; Neurophysiology ; Neurosciences ; Parkinson Disease

Schizophrenia is considered a neurodevelopmental disorder; however, all the available treatment options are used when the disease becomes clinically significant in adolescence or early adulthood. Using a developmental rat model of schizophrenia, we examined whether neonatal treatment with memantine, an NMDA receptor modulator, can improve schizophrenic-like symptoms in adulthood. Early maternal deprivation in rats produces deficits in social interaction behaviors in adulthood. In contrast, memantine administrated in neonatal rats subjected to early maternal deprivation significantly reduces deficits in social interaction behaviors in adulthood. These results raise the possibility that pharmacological treatment with memantine at the early developmental stage helps people with a risk to develop schizophrenic-like symptoms.
Adolescent ; Adult* ; Animals ; Cognition* ; Glutamic Acid ; Humans ; Interpersonal Relations ; Maternal Deprivation* ; Memantine* ; Models, Animal ; N-Methylaspartate ; Neurodevelopmental Disorders ; Neuropharmacology ; Rats* ; Schizophrenia

This article is to review neurobiology of attention-deficit/hyperactivity disorder (ADHD) and pharmacological properties of Osmotic-Controlled Release Oral delivery System Methylphenidate (OROS MPH)(Concerta Oros(R)) in celebration of its one-decade clinical experiences in Korea. ADHD is a highly heritable neurodevelopmental disorder, characterized by age-inappropriate inattention, hyperactivity and impulsiveness. The symptoms of ADHD are consistent with dysfunction of the prefrontal cortex (PFC). The PFC functions such as working memory and executive function are powerfully modulated by the catecholamine neurotransmitters, dopamine (DA) and norepinephrine (NE). Methylphenidate (MPH) is a first line treatment for children and adolescents with ADHD in Korea. MPH improves the PFC functions with the mechanism of action being modulation of DA and NE tones by blocking both dopamine transporter (DAT) and norepinephrine transporter (NET). Stimulation of D1 and NE alpha2 receptors on the postsynaptic neurons may be its main mechanisms of action which improve working memory and behavioral inhibition in patients with ADHD. OROS MPH, one of long-acting MPH, employs an osmotic-releasing oral system (OROS), which has been designed to have 12 hour duration of effect, which permits oncedaily dosing, which has been shown to be as effective as 3-times-a-day immediate-release formulation of MPH (IR MPH). Recently there is growing evidence that OROS MPH has positive effects even on adults with ADHD, in multidimensional aspects; cognitively, emotionally and functionally.
Adolescent ; Adult ; Child ; Dopamine ; Dopamine Plasma Membrane Transport Proteins ; Executive Function ; Humans ; Korea ; Memory, Short-Term ; Methylphenidate ; Neurobiology ; Neurons ; Neuropharmacology ; Neurotransmitter Agents ; Norepinephrine ; Norepinephrine Plasma Membrane Transport Proteins ; Phenazines ; Prefrontal Cortex

This article is to review neurobiology of attention-deficit/hyperactivity disorder (ADHD) and pharmacological properties of Osmotic-Controlled Release Oral delivery System Methylphenidate (OROS MPH)(Concerta Oros(R)) in celebration of its one-decade clinical experiences in Korea. ADHD is a highly heritable neurodevelopmental disorder, characterized by age-inappropriate inattention, hyperactivity and impulsiveness. The symptoms of ADHD are consistent with dysfunction of the prefrontal cortex (PFC). The PFC functions such as working memory and executive function are powerfully modulated by the catecholamine neurotransmitters, dopamine (DA) and norepinephrine (NE). Methylphenidate (MPH) is a first line treatment for children and adolescents with ADHD in Korea. MPH improves the PFC functions with the mechanism of action being modulation of DA and NE tones by blocking both dopamine transporter (DAT) and norepinephrine transporter (NET). Stimulation of D1 and NE alpha2 receptors on the postsynaptic neurons may be its main mechanisms of action which improve working memory and behavioral inhibition in patients with ADHD. OROS MPH, one of long-acting MPH, employs an osmotic-releasing oral system (OROS), which has been designed to have 12 hour duration of effect, which permits oncedaily dosing, which has been shown to be as effective as 3-times-a-day immediate-release formulation of MPH (IR MPH). Recently there is growing evidence that OROS MPH has positive effects even on adults with ADHD, in multidimensional aspects; cognitively, emotionally and functionally.
Adolescent ; Adult ; Child ; Dopamine ; Dopamine Plasma Membrane Transport Proteins ; Executive Function ; Humans ; Korea ; Memory, Short-Term ; Methylphenidate ; Neurobiology ; Neurons ; Neuropharmacology ; Neurotransmitter Agents ; Norepinephrine ; Norepinephrine Plasma Membrane Transport Proteins ; Phenazines ; Prefrontal Cortex

AIM: Trichosanthes dioica Roxb. (Cucurbitaceae), commonly known as pointed gourd in English, is a dioecious climber grown widely in the Indian subcontinent. Traditionally, this plant has been used in India for several medicinal purposes. The present study aimed to evaluate certain neuropharmacological properties of the hydroalcoholic extract of T. dioica root (TDA) in experimental animal models. METHODS: TDA (at 100 and 200 mg·kg(-1) body weight, p.o.) was evaluated for anti-nociceptive activity by the acetic acid-induced writhing and tail flick methods. Locomotor depressant activity was measured by means of an actophotometer. Skeletal muscle relaxant effects were evaluated by using a rota-rod apparatus, and the sedative potentiating property by a phenobarbitone-induced sleep potentiation study. RESULTS: The results of the present study revealed significant (P < 0.001) and dose dependent anti-nociceptive, locomotor depressant, muscle relaxant, and sedative potentiating effects of TDA, demonstrating its depressant action on the central nervous system (CNS). CONCLUSION From the present study, it can be concluded that T. dioica root possessed prominent anti-nociceptive, as well as depressant, action on the CNS, as manifested by these important neuropharmacological properties in mice.
Analgesics ; administration & dosage ; Animals ; Central Nervous System Diseases ; drug therapy ; physiopathology ; Humans ; India ; Male ; Mice ; Muscle Relaxants, Central ; administration & dosage ; Muscle Relaxation ; drug effects ; Neuropharmacology ; Plant Extracts ; administration & dosage ; Plant Roots ; chemistry ; Trichosanthes ; chemistry

OBJECTIVETo re-confirm and characterize the biophysical and pharmacological properties of endogenously expressed human acid-sensing ion channel 1a (hASIC1a) current in HEK293 cells with a modified perfusion methods.

METHODSWith cell floating method, which is separating the cultured cell from coverslip and putting the cell in front of perfusion tubing, whole cell patch clamp technique was used to record hASIC1a currents evoked by low pH external solution.

RESULTSUsing cell floating method, the amplitude of hASIC1a currents activated by pH 5.0 in HEK293 cells is twice as large as that by the conventional method where the cells remain attached to coverslip. The time to reach peak at two different recording conditions is (21+/-5) ms and (270+/-25) ms, respectively. Inactivation time constants are (496+/-23) ms and (2284+/-120) ms, respectively. The cell floating method significantly increases the amiloride potency of block on hASIC1a [IC50 is (3.4+/-1.1) micromol/L and (2.4+/- 0.9) micromol/L, respectively]. Both recording methods have similar pH activation EC50 (6.6+/-0.6, 6.6+/-0.7, respectively).

CONCLUSIONASICs channel activation requires fast exchange of extracellular solution with the different pH values. With cell floating method, the presence of hASIC1a current was re-confirmed and the biophysical and pharmacological properties of hASIC1a channel in HEK293 cells were precisely characterized. This method could be used to study all ASICs and other ligand-gated channels that require fast extracellular solution exchange.

Acid Sensing Ion Channels ; Amiloride ; pharmacology ; Biophysics ; instrumentation ; methods ; Cell Culture Techniques ; instrumentation ; methods ; Cell Line ; Cell Membrane ; chemistry ; drug effects ; metabolism ; Culture Media ; chemistry ; pharmacology ; Extracellular Fluid ; chemistry ; metabolism ; Humans ; Hydrogen-Ion Concentration ; drug effects ; Membrane Potentials ; drug effects ; physiology ; Nerve Tissue Proteins ; chemistry ; drug effects ; metabolism ; Neuropharmacology ; instrumentation ; methods ; Patch-Clamp Techniques ; instrumentation ; methods ; Perfusion ; instrumentation ; methods ; Sodium Channel Blockers ; pharmacology ; Sodium Channels ; chemistry ; drug effects ; metabolism ; Time Factors