dextromethorphan and Syndrome

Dextromethorphan, a noncompetitive blocker of the N-methyl-D-aspartate (NMDA) type of glutamate receptor, at 45, 60 and 75 mg/kg, ip doses induced a behavioural syndrome characterised by reciprocal forepaw treading, lateral head-weaving, hind-limb abduction and flat body posture. Such type of behavioural syndrome is induced by 8-hydroxy-2- (di-n-propylamino) tetralin (8-OH-DPAT) by directly stimulating the central postsynaptic 5-hydroxytryptamine (5-HT, serotonin) receptors of the 5-HT1A type. Pretreatment with buspirone (5, 10 mg/kg, ip) and l-propranolol (10, 20 mg/kg, ip) antagonised the behavioural syndrome induced by 8-OH-DPAT and dextromethorphan. Pretreatment with p-chlorophenylalanine (100 mg/kg/day x 4 days) antagonised the behavioural syndrome induced by dextromethorphan and dexfenfluramine but had no significant effect on 8-OH-DPAT induced behavioural syndrome. This indicates that dextromethorphan induces the behavioural syndrome by releasing 5-HT from serotonergic neurons with resultant activation of the postsynaptic 5-HT1A receptors by the released 5-HT. Pretreatment with fluoxetine (10 mg/kg, ip) significantly potentiated the behavioural syndrome induced by dextromethorphan and 5-hydroxytryptophan but significantly antagonised dexfenfluramine induced behavioural syndrome. This indicates that dextromethorphan releases 5-HT by a mechanism which differs from that of dexfenfluramine. Dextromethorphan may be releasing 5-HT by blocking the NMDA receptors and thereby counteracting the inhibitory influence of l-glutamate on 5-HT release.

Topics: 8-Hydroxy-2-(di-n-propylamino)tetralin; Animals; Antitussive Agents; Behavior, Animal; Buspirone; Central Nervous System; Dexfenfluramine; Dextromethorphan; Fluoxetine; Male; Propranolol; Rats; Rats, Wistar; Serotonin; Serotonin Receptor Agonists; Syndrome

Topics: Cytochrome P-450 CYP2D6; Cytochrome P-450 Enzyme Inhibitors; Dextromethorphan; Drug Interactions; Female; Humans; Mixed Function Oxygenases; Paroxetine; Serotonin; Syndrome

Topics: 1-Naphthylamine; Adult; Dextromethorphan; Drug Therapy, Combination; Female; Humans; Isocarboxazid; Methylphenidate; Neurologic Examination; Neuromuscular Diseases; Selective Serotonin Reuptake Inhibitors; Serotonin; Sertraline; Syndrome; Trazodone

There is a new, potentially fatal disorder that is infrequently reported. The apparent rareness may be because of a lack of recognition of the syndrome or its predisposing factors. Fluoxetine (Prozac, Dista Products Co, Division of Eli Lilly Co, Indianapolis, IN), sertraline (Zoloft, Roerig Division, Pfizer Inc, New York, NY), and paroxetine (Paxil, SmithKline Beecham Pharmaceuticals, Philadelphia, PA) belong to a new class of antidepressant medication: the serotonin reuptake-inhibitors (SRIs). The relative safety profile of the SRIs has led to their widespread use. However, a syndrome of excessive serotonergic activity, the "serotonin syndrome" (SS), has recently been recognized. It is characterized by changes in mental status, hypertension, restlessness, myoclonus, hyperreflexia, diaphoresis, shivering, and tremor. A high index of suspicion is required to make the diagnosis in these acutely ill patients. The most common agents implicated in SS are the monoamine oxidase inhibitors in combination with L-tryptophan or fluoxetine. A case of a patient with significant peripheral vascular disease who developed SS while taking paroxetine and an over-the-counter cold medicine is reported. There have been no prior reports of this interaction. Discontinuation of the offending agents, sedation, and supportive care are the mainstays of treatment. The interactions of serotonin with platelets and vascular endothelium are also discussed.

Topics: Acetaminophen; Acute Disease; Akathisia, Drug-Induced; Blood Platelets; Dextromethorphan; Diagnosis, Differential; Doxylamine; Drug Combinations; Drug Interactions; Drug Therapy, Combination; Endothelium, Vascular; Ephedrine; Humans; Hypertension; Male; Middle Aged; Myoclonus; Nonprescription Drugs; Paroxetine; Peripheral Vascular Diseases; Promethazine; Pseudoephedrine; Sweating; Syndrome

Topics: Adult; Central Nervous System; Clomipramine; Depressive Disorder; Dextromethorphan; Drug Interactions; Drug Overdose; Emergencies; Female; Humans; Phenelzine; Serotonin; Syndrome