Pharmacology
Pharmacodynamics
Dextromethorphan has been found to possess the following actions (<1 μM) using rat tissues:
Uncompetitive antagonist of the NMDA receptor via the MK-801/PCP site
SERT and NET blocker (cf. serotonin–norepinephrine reuptake inhibitor)
Sigma σ1 receptor agonist
Negative allosteric modulator of nicotinic acetylcholine receptors
Ligand of the serotonin 5-HT1B/1D, histamine H1, α2-adrenergic, and muscarinic acetylcholine receptorsDextromethorphan is a prodrug of dextrorphan, which is the actual mediator of most of its dissociative effects through acting as a more potent NMDA receptor antagonist than dextromethorphan itself. What role, if any, (+)-3-methoxymorphinan, dextromethorphans other major metabolite, plays in its effects is not entirely clear. Pharmacokinetics
Following oral administration, dextromethorphan is rapidly absorbed from the gastrointestinal tract, where it enters the bloodstream and crosses the blood–brain barrier.At therapeutic doses, dextromethorphan acts centrally (meaning that it acts on the brain) as opposed to locally (on the respiratory tract). It elevates the threshold for coughing, without inhibiting ciliary activity. Dextromethorphan is rapidly absorbed from the gastrointestinal tract and converted into the active metabolite dextrorphan in the liver by the cytochrome P450 enzyme CYP2D6. The average dose necessary for effective antitussive therapy is between 10 and 45 mg, depending on the individual. The International Society for the Study of Cough recommends "an adequate first dose of medication is 60 mg in the adult and repeat dosing should be infrequent rather than qds recommended. "Dextromethorphan has an elimination half-life of approximately 4 hours in individuals with an extensive metabolizer phenotype; this is increased to approximately 13 hours when dextromethorphan is given in combination with quinidine.
Psychasthenia was a psychological disorder characterized by phobias, obsessions, compulsions, or excessive anxiety. The term is no longer in psychiatric diagnostic use, although it still forms one of the ten clinical subscales of the popular self-report personality inventories MMPI and MMPI-2. Signs and symptoms
The MMPI subscale 7 describes psychasthenia as akin to obsessive-compulsive disorder, and as characterised by excessive doubts, compulsions, obsessions, and unreasonable fears. The psychasthenic has an inability to resist specific actions or thoughts, regardless of their maladaptive nature. In addition to obsessive-compulsive features, the scale taps abnormal fears, self-criticism, difficulties in concentration, and guilt feelings. The scale assesses long-term (trait) anxiety, although it is somewhat responsive to situational stress as well. The psychasthenic has insufficient control over their conscious thinking and memory, sometimes wandering aimlessly and/or forgetting what they were doing. Thoughts can be scattered and take significant effort to organize, often resulting in sentences that do not come out as intended, therefore making little sense to others. The constant mental effort and characteristic insomnia induces fatigue, which worsens the condition. Symptoms can possibly be greatly reduced with concentration exercises and therapy, depending on whether the condition is psychological or biological. History
The term "psychasthenia" is historically associated primarily with the work of Pierre Janet, who divided the neuroses into the psychasthenias and the hysterias, discarding the term "neurasthenia" since it implied a neurological theory where none existed.