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    | Mechanism of Action | 
    
       Carbinoxamine¿¡ ´ëÇÑ Mechanism_Of_Action Á¤º¸ Carbinoxamine competes with free histamine for binding at HA-receptor sites. This antagonizes the effects of histamine on HA-receptors, leading to a reduction of the negative symptoms brought on by histamine HA-receptor binding. Carbinoxamine's anticholinergic action appears to be due to a central antimuscarinic effect, which also may be responsible for its antiemetic effects, although the exact mechanism is unknown.
  Dextromethorphan¿¡ ´ëÇÑ Mechanism_Of_Action Á¤º¸ Dextromethorphan is an opioid-like drug that binds to and acts as antagonist to the NMDA glutamatergic receptor, it is an agonist to the opioid sigma 1 and sigma 2 receptors, it is also an alpha3/beta4 nicotinic receptor antagonist and targets the serotonin reuptake pump. Dextromethorphan is rapidly absorbed from the gastrointestinal tract, where it enters the bloodstream and crosses the blood-brain barrier. The first-pass through the hepatic portal vein results in some of the drug being metabolized into an active metabolite of dextromethorphan, dextrorphan, the 3-hydroxy derivative of dextromethorphan.
  Phenylpropanolamine¿¡ ´ëÇÑ Mechanism_Of_Action Á¤º¸ Phenylpropanolamine acts directly on alpha- and, to a lesser degree, beta-adrenergic receptors in the mucosa of the respiratory tract. Stimulation of alpha-adrenergic receptors produces vasoconstriction, reduces tissue hyperemia, edema, and nasal congestion, and increases nasal airway patency. PPA indirectly stimulates beta-receptors, producing tachycardia and a positive inotropic effect. 
     | 
   
  
   
    | Pharmacology | 
     
       Carbinoxamine¿¡ ´ëÇÑ Pharmacology Á¤º¸ Carbinoxamine is an antihistamine of the ethanolamine class. Ethanolamine antihistamines have significant antimuscarinic activity and produce marked sedation in most patients. In addition to the usual allergic symptoms, the drug also treats irritant cough and nausea, vomiting, and vertigo associated with motion sickness. It also is used commonly to treat drug-induced extrapyramidal symptoms as well as to treat mild cases of Parkinson's disease. Rather than preventing the release of histamine, as do cromolyn and nedocromil, carbinoxamine competes with free histamine for binding at HA-receptor sites. Carbinoxamine competitively antagonizes the effects of histamine on HA-receptors in the GI tract, uterus, large blood vessels, and bronchial muscle. Ethanolamine derivatives have greater anticholinergic activity than do other antihistamines, which probably accounts for the antidyskinetic action of carbinoxamine.
  Dextromethorphan¿¡ ´ëÇÑ Pharmacology Á¤º¸ Dextromethorphan suppresses the cough reflex by a direct action on the cough center in the medulla of the brain. Dextromethorphan shows high affinity binding to several regions of the brain, including the medullary cough center. This compound is an NMDA receptor antagonist and acts as a non-competitive channel blocker. It is one of the widely used antitussives, and is also used to study the involvement of glutamate receptors in neurotoxicity.
  Phenylpropanolamine¿¡ ´ëÇÑ Pharmacology Á¤º¸ Phenylpropanolamine (PPA), a sympathomimetic agent structurally similar to pseudoephedrine, is used to treat nasal congestion. Phenylpropanolamine is found in appetite suppressant formulations and with guaifenesinin in cough-cold formulations. In 2000, the FDA requested that all drug companies discontinue marketing products containing phenylpropanolamine, due to an increased risk of hemorrhagic stroke in women who used phenylpropanolamine. 
     | 
   
  
   
    | Metabolism | 
    
       Dextromethorphan¿¡ ´ëÇÑ Metabolism Á¤º¸ # Phase_1_Metabolizing_Enzyme:Cytochrome P450 2D6 (CYP2D6)
  Phenylpropanolamine¿¡ ´ëÇÑ Metabolism Á¤º¸ # Phase_1_Metabolizing_Enzyme:Monoamine oxidase type A (MAO-A) 
     | 
   
  
   
    | Protein Binding | 
    
       Phenylpropanolamine¿¡ ´ëÇÑ ´Ü¹é°áÇÕ Á¤º¸ Not Available 
     | 
   
  
   
    | Half-life | 
    
       Carbinoxamine¿¡ ´ëÇÑ ¹Ý°¨±â Á¤º¸ 10 to 20 hours
  Dextromethorphan¿¡ ´ëÇÑ ¹Ý°¨±â Á¤º¸ 3-6 hours
  Phenylpropanolamine¿¡ ´ëÇÑ ¹Ý°¨±â Á¤º¸ 2.1 to 3.4 hours. 
     | 
   
  
   
    | Absorption | 
    
       Dextromethorphan¿¡ ´ëÇÑ Absorption Á¤º¸ Rapidly absorbed from the gastrointestinal tract.
  Phenylpropanolamine¿¡ ´ëÇÑ Absorption Á¤º¸ Reduced bioavailability (about 38%) from gastrointestinal tract because of first pass metabolism by monoamine oxidase in the stomach and liver. 
     | 
   
  
   
    | Pharmacokinetics | 
    
       Carbinoxamine MaleateÀÇ ¾à¹°µ¿·ÂÇÐÀÚ·á 
- ÀÛ¿ëÁö¼Ó½Ã°£ : 3-6 ½Ã°£
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 Dextromethorphan HBrÀÇ ¾à¹°µ¿·ÂÇÐÀÚ·á 
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 Phenylpropanolamine HClÀÇ ¾à¹°µ¿·ÂÇÐÀÚ·á 
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	 -  »ýü³»ÀÌ¿ë·ü : °ÅÀÇ 100%
 
	 -  ´ë»ç : °£¿¡¼ norephedrineÀ¸·Î ´ë»çµÊ
 
	 -  ¹Ý°¨±â : 4.6-6.6 ½Ã°£ 
 
	 -  ¼Ò½Ç : ÁÖ·Î ¹Ìº¯Èü·Î¼(80-90%) ´¢¸¦ ÅëÇØ ¹è¼³µÊ
  
     | 
   
  
   
    | Biotransformation | 
    
       Dextromethorphan¿¡ ´ëÇÑ Biotransformation Á¤º¸ Hepatic. Rapidly and extensively metabolized to dextrorphan (active metabolite). One well known metabolic catalyst involved is a specific cytochrome P450 enzyme known as 2D6, or CYP2D6.
  Phenylpropanolamine¿¡ ´ëÇÑ Biotransformation Á¤º¸ Hepatic 
     | 
   
  
   
    | Toxicity | 
    
       Dextromethorphan¿¡ ´ëÇÑ Toxicity Á¤º¸ Not Available
  Phenylpropanolamine¿¡ ´ëÇÑ Toxicity Á¤º¸ May induce ventricular extrasystoles and short paroxysms of ventricular tachycardia, a sensation of fullness in the head and tingling of the extremities; LD50=1490mg/kg (orally in rat) 
     | 
   
  
   
    | Drug Interactions | 
    
       Dextromethorphan¿¡ ´ëÇÑ Drug_Interactions Á¤º¸ Dihydroquinidine barbiturate	Quinidine increases the toxicity of dextromethorphanQuinidine	Quinidine increases the toxicity of dextromethorphanQuinidine barbiturate	Quinidine increases the toxicity of dextromethorphanFluoxetine	Combination associated with possible serotoninergic syndromeIsocarboxazid	Possible severe adverse reactionMemantine	Increased risk of CNS adverse effectsMoclobemide	Increased CNS toxicityParoxetine	Combination associated with possible serotoninergic syndromePhenelzine	Possible severe adverse reactionRasagiline	Possible severe adverse reactionSelegiline	Combination associated with possible serotoninergic syndromeSibutramine	Combination associated with possible serotoninergic syndromeTerbinafine	Terbinafine increases dextromethorphan levelsTranylcypromine	Possible severe adverse reaction
  Phenylpropanolamine¿¡ ´ëÇÑ Drug_Interactions Á¤º¸ Acetophenazine	Decreased anorexic effect, may increase psychotic symptomsChlorpromazine	Decreased anorexic effect, may increase psychotic symptomsEthopropazine	Decreased anorexic effect, may increase psychotic symptomsFluphenazine	Decreased anorexic effect, may increase psychotic symptomsMethotrimeprazine	Decreased anorexic effect, may increase psychotic symptomsGuanethidine	The agent decreases the effect of guanethidineMesoridazine	Decreased anorexic effect, may increase psychotic symptomsThioridazine	Decreased anorexic effect, may increase psychotic symptomsMethdilazine	Decreased anorexic effect, may increase psychotic symptomsTrimeprazine	Decreased anorexic effect, may increase psychotic symptomsPropericiazine	Decreased anorexic effect, may increase psychotic symptomsPerphenazine	Decreased anorexic effect, may increase psychotic symptomsProchlorperazine	Decreased anorexic effect, may increase psychotic symptomsPromazine	Decreased anorexic effect, may increase psychotic symptomsPromethazine	Decreased anorexic effect, may increase psychotic symptomsPropiomazine	Decreased anorexic effect, may increase psychotic symptomsThiethylperazine	Decreased anorexic effect, may increase psychotic symptomsTrifluoperazine	Decreased anorexic effect, may increase psychotic symptomsTriflupromazine	Decreased anorexic effect, may increase psychotic symptomsMoclobemide	Moclobemide increases the sympathomimetic effectAmitriptyline	The tricyclic increases the sympathomimetic effectAmoxapine	The tricyclic increases the sympathomimetic effectBromocriptine	The sympathomimetic increases the toxicity of bromocriptineClomipramine	The tricyclic increases the sympathomimetic effectDesipramine	The tricyclic increases the sympathomimetic effectDoxepin	The tricyclic increases the sympathomimetic effectImipramine	The tricyclic increases the sympathomimetic effectNortriptyline	The tricyclic increases the sympathomimetic effectProtriptyline	The tricyclic increases the sympathomimetic effectTrimipramine	The tricyclic increases the sympathomimetic effectVenlafaxine	Risk of serotoninergic syndromeFluvoxamine	Risk of serotoninergic syndromeParoxetine	Risk of serotoninergic syndromeFluoxetine	Risk of serotoninergic syndromeAlseroxylon	Increased arterial pressureDeserpidine	Increased arterial pressureIsocarboxazid	Increased arterial pressureLinezolid	Possible increase of arterial pressureTranylcypromine	Increased arterial pressureRasagiline	Increased arterial pressureReserpine	Increased arterial pressurePhenelzine	Increased arterial pressurePargyline	Increased arterial pressureMethyldopa	Increased arterial pressureMidodrine	Increased arterial pressure 
     | 
   
  
   
    CYP450  Drug Interaction | 
    
      [CYP450 TableÁ÷Á¢Á¶È¸] Dextromethorphan¿¡ ´ëÇÑ P450 table
  SUBSTRATES 
CYP 2D6 
Beta Blockers: 
S-metoprolol 
propafenone 
timolol 
Antidepressants: 
amitriptyline 
clomipramine 
desipramine 
imipramine 
paroxetine 
Antipsychotics: 
haloperidol 
risperidone 
thioridazine 
aripiprazole 
codeine 
**dextromethorphan** 
duloxetine 
flecainide 
mexiletine 
ondansetron 
tamoxifen 
tramadol 
venlafaxine 
 INHIBITORS 
CYP 2D6 
amiodarone 
buproprion 
chlorpheniramine 
cimetidine 
clomipramine 
duloxetine 
fluoxetine 
haloperidol 
methadone 
mibefradil 
paroxetine 
quinidine 
ritonavir 
 INDUCERS 
CYP 2D6 
N/A 
 
     | 
   
  
   
    | Food Interaction | 
    
       Phenylpropanolamine¿¡ ´ëÇÑ Food Interaction Á¤º¸ Take without regard to meals.Limit caffeine intake. 
     | 
   
  
   
    | Drug Target | 
    
      
      [Drug Target]
     | 
   
  
   
    | SNP Á¤º¸ | 
    
      Name:Dextromethorphan (DB00514)
 Interacting Gene/Enzyme:Cytochrome P450 2D6 (Gene symbol = CYP2D6) Swissprot P10635
 SNP(s):CYP2D6*6 rs5030655 (T deletion, homozygote)
 Effect:Poor drug metabolizer, lower dose requirements
 Reference(s):Bradford LD, Gaedigk A, Leeder JS: High frequency of CYP2D6 poor and "intermediate" metabolizers in black populations: a review and preliminary data. Psychopharmacol Bull. 1998;34(4):797-804. [PubMed] 
     | 
   
  
   
    | Description | 
    
       Carbinoxamine¿¡ ´ëÇÑ Description Á¤º¸ Carbinoxamine competes with free histamine for binding at HA-receptor sites. This antagonizes the effects of histamine on HA-receptors, leading to a reduction of the negative symptoms brought on by histamine HA-receptor binding. In addition to the usual allergic symptoms, the drug also treats irritant cough and nausea, vomiting, and vertigo associated with motion sickness. Carbinoxamine's anticholinergic action appears to be due to a central antimuscarinic effect, which also may be responsible for its antiemetic effects, although the exact mechanism is unknown. It also is used commonly to treat drug-induced extrapyramidal symptoms as well as to treat mild cases of Parkinson's disease.
  Dextromethorphan¿¡ ´ëÇÑ Description Á¤º¸ The d-isomer of the codeine analog of levorphanol. Dextromethorphan shows high affinity binding to several regions of the brain, including the medullary cough center. This compound is an NMDA receptor antagonist (receptors, N-methyl-D-aspartate) and acts as a non-competitive channel blocker. It is one of the widely used antitussives, and is also used to study the involvement of glutamate receptors in neurotoxicity. [PubChem]
  Phenylpropanolamine¿¡ ´ëÇÑ Description Á¤º¸ Phenylpropanolamine has been withdrawn in Canada. In November 2000, the Food and Drug Administration (FDA) issued a public health advisory against the use of the drug. 
     | 
   
  
   
    | Dosage Form | 
    
       Carbinoxamine¿¡ ´ëÇÑ Dosage_Form Á¤º¸ Solution / drops	OralSyrup	OralTablet	OralTablet, extended release	Oral
  Dextromethorphan¿¡ ´ëÇÑ Dosage_Form Á¤º¸ Capsule	OralLiquid	OralLozenge	OralStrip	OralSuspension	OralSyrup	OralTablet	Oral
  Phenylpropanolamine¿¡ ´ëÇÑ Dosage_Form Á¤º¸ Not Available 
     | 
   
  
   
    | Drug Category | 
    
       Carbinoxamine¿¡ ´ëÇÑ Drug_Category Á¤º¸ Antihistamines
  Dextromethorphan¿¡ ´ëÇÑ Drug_Category Á¤º¸ Analgesics, OpioidAntitussive AgentsExcitatory Amino Acid Antagonists
  Phenylpropanolamine¿¡ ´ëÇÑ Drug_Category Á¤º¸ Adrenergic alpha-AgonistsAppetite DepressantsNasal DecongestantsSympathomimetics 
     | 
   
  
   
    | Smiles String Canonical | 
    
       Carbinoxamine¿¡ ´ëÇÑ Smiles_String_canonical Á¤º¸ CN(C)CCOC(C1=CC=C(Cl)C=C1)C1=CC=CC=N1
  Dextromethorphan¿¡ ´ëÇÑ Smiles_String_canonical Á¤º¸ COC1=CC2=C(CC3C4CCCCC24CCN3C)C=C1
  Phenylpropanolamine¿¡ ´ëÇÑ Smiles_String_canonical Á¤º¸ CC(N)C(O)C1=CC=CC=C1 
     | 
   
  
   
    | Smiles String Isomeric | 
    
       Carbinoxamine¿¡ ´ëÇÑ Smiles_String_isomeric Á¤º¸ CN(C)CCO[C@@H](C1=CC=C(Cl)C=C1)C1=CC=CC=N1
  Dextromethorphan¿¡ ´ëÇÑ Smiles_String_isomeric Á¤º¸ COC1=CC2=C(C[C@H]3[C@H]4CCCC[C@@]24CCN3C)C=C1
  Phenylpropanolamine¿¡ ´ëÇÑ Smiles_String_isomeric Á¤º¸ C[C@@H](N)[C@@H](O)C1=CC=CC=C1 
     | 
   
  
   
    | InChI Identifier | 
    
       Carbinoxamine¿¡ ´ëÇÑ InChI_Identifier Á¤º¸ InChI=1/C16H19ClN2O/c1-19(2)11-12-20-16(15-5-3-4-10-18-15)13-6-8-14(17)9-7-13/h3-10,16H,11-12H2,1-2H3
  Dextromethorphan¿¡ ´ëÇÑ InChI_Identifier Á¤º¸ InChI=1/C18H25NO/c1-19-10-9-18-8-4-3-5-15(18)17(19)11-13-6-7-14(20-2)12-16(13)18/h6-7,12,15,17H,3-5,8-11H2,1-2H3/t15-,17+,18-/m1/s1
  Phenylpropanolamine¿¡ ´ëÇÑ InChI_Identifier Á¤º¸ InChI=1/C9H13NO/c1-7(10)9(11)8-5-3-2-4-6-8/h2-7,9,11H,10H2,1H3/t7-,9-/m1/s1 
     | 
   
  
   
    | Chemical IUPAC Name | 
    
       Carbinoxamine¿¡ ´ëÇÑ Chemical_IUPAC_Name Á¤º¸ 2-[(4-chlorophenyl)-pyridin-2-ylmethoxy]-N,N-dimethylethanamine
  Dextromethorphan¿¡ ´ëÇÑ Chemical_IUPAC_Name Á¤º¸ Not Available
  Phenylpropanolamine¿¡ ´ëÇÑ Chemical_IUPAC_Name Á¤º¸ (1S,2R)-2-amino-1-phenylpropan-1-ol 
     | 
   
  
   
    | Drug-Induced Toxicity Related Proteins | 
    
      MALEATE ÀÇ Drug-Induced Toxicity Related ProteinÁ¤º¸ Replated Protein:Intercellular adhesion molecule 1  Drug:maleate Toxicity:hepatic injury.  [¹Ù·Î°¡±â] 
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