zimeldine and Seizures

The side effect profile and safety of fluoxetine are reviewed. Side effects reported more frequently with fluoxetine than with tricyclic antidepressants are nausea, nervousness, and insomnia. Anticholinergic side effects are reported less often with fluoxetine. Analysis of adverse experiences leading to discontinuations suggests that this drug has very few serious side effects. There is no evidence that fluoxetine produces a flu-like syndrome or neuropathy similar to that seen with zimelidine. It does not appear to cause phospholipidosis in humans. Fluoxetine appears to have no epileptogenic potential except at extremely high doses. It is usually well tolerated in overdoses.

Topics: Adult; Akathisia, Drug-Induced; Antidepressive Agents, Tricyclic; Cardiovascular Diseases; Clinical Trials as Topic; Drug Eruptions; Female; Fluoxetine; Humans; Influenza, Human; Lipidoses; Male; Middle Aged; Nausea; Nervous System Diseases; Patient Dropouts; Phospholipids; Placebos; Propylamines; Psychoses, Substance-Induced; Seizures; Sleep Initiation and Maintenance Disorders; Suicide, Attempted; Vision Disorders; Zimeldine

The host of newly developed antidepressant drugs offer important clinical advantages to some patients, although their promises of improved therapeutic efficacy and reduced adverse effects compared with conventional treatments are not fully realized. Increased biochemical specificity and unique mechanistic or clinical profiles render these compounds valuable in research into the pathophysiology of affective disorders and mode of action of antidepressant agents.

Topics: Alprazolam; Amoxapine; Antidepressive Agents; Benzodiazepines; Bupropion; Citalopram; Clinical Trials as Topic; Dopamine; Double-Blind Method; Humans; Maprotiline; Nomifensine; Norepinephrine; Propiophenones; Propylamines; Seizures; Serotonin; Trazodone; Zimeldine

The side effect profile and safety of fluoxetine are reviewed. Side effects reported more frequently with fluoxetine than with tricyclic antidepressants are nausea, nervousness, and insomnia. Anticholinergic side effects are reported less often with fluoxetine. Analysis of adverse experiences leading to discontinuations suggests that this drug has very few serious side effects. There is no evidence that fluoxetine produces a flu-like syndrome or neuropathy similar to that seen with zimelidine. It does not appear to cause phospholipidosis in humans. Fluoxetine appears to have no epileptogenic potential except at extremely high doses. It is usually well tolerated in overdoses.

Topics: Adult; Akathisia, Drug-Induced; Antidepressive Agents, Tricyclic; Cardiovascular Diseases; Clinical Trials as Topic; Drug Eruptions; Female; Fluoxetine; Humans; Influenza, Human; Lipidoses; Male; Middle Aged; Nausea; Nervous System Diseases; Patient Dropouts; Phospholipids; Placebos; Propylamines; Psychoses, Substance-Induced; Seizures; Sleep Initiation and Maintenance Disorders; Suicide, Attempted; Vision Disorders; Zimeldine

The host of newly developed antidepressant drugs offer important clinical advantages to some patients, although their promises of improved therapeutic efficacy and reduced adverse effects compared with conventional treatments are not fully realized. Increased biochemical specificity and unique mechanistic or clinical profiles render these compounds valuable in research into the pathophysiology of affective disorders and mode of action of antidepressant agents.

Topics: Alprazolam; Amoxapine; Antidepressive Agents; Benzodiazepines; Bupropion; Citalopram; Clinical Trials as Topic; Dopamine; Double-Blind Method; Humans; Maprotiline; Nomifensine; Norepinephrine; Propiophenones; Propylamines; Seizures; Serotonin; Trazodone; Zimeldine

To further evaluate whether selective serotonin reuptake inhibitors (SSRIs) have pro- or anticonvulsant properties and whether these properties will be modified by stress, we studied the effect of zimelidine on the convulsions produced by picrotoxin, a GABA(A) receptor antagonist, in unstressed and swim stressed mice. Zimelidine potentiated the ability of swim stress to enhance the threshold doses of intravenously administered picrotoxin producing convulsant signs and death, without having an effect in unstressed mice. The anticonvulsant effect of zimelidine was counteracted with mianserin, the antagonist of 5-HT(2A/2C), and diminished with WAY-100635, a selective antagonist of 5-HT(1A) receptors. In stressed mice, WAY-100635 prevented the anticonvulsant effect of 8-OH-DPAT, a 5-HT(1A) receptor agonist. SB-269970 and ketanserin, the antagonists of 5-HT(7) and 5-HT(2A) receptors, respectively, failed to reduce the effect of zimelidine. The results suggest the involvement of 5-HT(2C) and 5-HT(1A) receptors in the anticonvulsant effects of zimelidine and possibly other SSRIs in stress.

Topics: 8-Hydroxy-2-(di-n-propylamino)tetralin; Animals; Anticonvulsants; Behavior, Animal; Convulsants; Ketanserin; Male; Mianserin; Mice; Mice, Inbred CBA; Phenols; Picrotoxin; Piperazines; Pyridines; Seizures; Selective Serotonin Reuptake Inhibitors; Serotonin Antagonists; Serotonin Receptor Agonists; Stress, Psychological; Sulfonamides; Swimming; Zimeldine

Research has shown a synergistic relationship between amphetamine sensitization and limbic system kindling. To explore the role of GABA and NMDA receptor activity in modulating the positive effects of amphetamine on epileptogenesis, alterations in GABA- and NMDA-related convulsions were examined after acute and chronic amphetamine administration. A single injection of d-amphetamine (7.5 mg/kg) significantly decreased latencies to generalized motor seizures induced 12 h later by the noncompetitive GABAA receptor antagonist picrotoxin (10 mg/kg). The increased sensitivity to clonus was specific to acute amphetamine treatment and was not evident following withdrawal from chronic drug exposure. Seizures induced by NMDLA (1,000 mg/kg), on the other hand, were not modified by acute amphetamine injection; however, the latency to clonus was reduced substantially after NMDLA injection to mice chronically preexposed to amphetamine. The short- and long-term amphetamine effects on GABA- and NMDA-associated convulsive activity were not paralleled by similar drug treatment schedules involving acute (20 mg/kg) and chronic administration of desipramine, zimelidine, and buproprion. These results suggest that amphetamine may be acting on inhibitory and excitatory amino acid systems independently of its monoaminergic properties. The implications of these findings were discussed in relation to amphetamine sensitization of mesolimbic functioning.

Topics: Amphetamine; Animals; Antidepressive Agents; Bupropion; Desipramine; Male; Mice; N-Methylaspartate; Picrotoxin; Receptors, GABA-A; Receptors, N-Methyl-D-Aspartate; Seizures; Zimeldine