Identification

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Name
Buclizine
Accession Number
DB00354  (APRD00723)
Type
Small Molecule
Groups
Approved
Description

Buclizine is an antihistamine medication with both antiemetic and anticholinergic effects 5, belonging to the piperazine derivative family of drugs. It was manufactured by Stuart Pharms and initially approved by the FDA in 1957.4 Following this, it was touted to be effective as an appetite stimulant in children when administered in the syrup form, however, this indication has not been validated.1 In addition to the above conditions, buclizine has been studied in the treatment of migraine attacks and in the treatment of nausea and vomiting during pregnancy. 2,3

Structure
Thumb
Synonyms
  • 1-(p-tert-Butylbenzyl)-4-(4-chloro-alpha-phenylbenzyl)piperazine
  • Buclizina
  • Buclizine
  • Buclizinum
Product Ingredients
IngredientUNIICASInChI Key
Buclizine hydrochloride58FQD093NU129-74-8SDBHDSZKNVDKNU-UHFFFAOYSA-N
International/Other Brands
Bucladin / Bucladin-S / Longifene Syrup (Novartis India)
Categories
UNII
0C94V6X681
CAS number
82-95-1
Weight
Average: 433.028
Monoisotopic: 432.233226773
Chemical Formula
C28H33ClN2
InChI Key
MOYGZHXDRJNJEP-UHFFFAOYSA-N
InChI
InChI=1S/C28H33ClN2/c1-28(2,3)25-13-9-22(10-14-25)21-30-17-19-31(20-18-30)27(23-7-5-4-6-8-23)24-11-15-26(29)16-12-24/h4-16,27H,17-21H2,1-3H3
IUPAC Name
1-[(4-tert-butylphenyl)methyl]-4-[(4-chlorophenyl)(phenyl)methyl]piperazine
SMILES
CC(C)(C)C1=CC=C(CN2CCN(CC2)C(C2=CC=CC=C2)C2=CC=C(Cl)C=C2)C=C1

Pharmacology

Indication

For prevention and treatment of nausea, vomiting, and dizziness associated with motion sickness and vertigo (dizziness caused by other medical problems).

Pharmacodynamics

Buclizine is a piperazine-derivative antihistamine used as an antivertigo/antiemetic agent. Buclizine is used in the prevention and treatment of nausea, vomiting, and dizziness associated with motion sickness. Additionally, it has been used in the management of vertigo in diseases affecting the vestibular apparatus. Although the mechanism by which buclizine exerts its antiemetic and antivertigo effects has not been fully elucidated, its central anticholinergic properties are partially responsible. The drug depresses labyrinth excitability and vestibular stimulation, and it may affect the medullary chemoreceptor trigger zone. It also possesses anticholinergic, antihistaminic, central nervous system depressant, and local anesthetic effects.

Mechanism of action

Vomiting (emesis) is essentially a protective mechanism for removing irritant or otherwise harmful substances from the upper GI tract. Emesis or vomiting is controlled by the vomiting centre in the medulla region of the brain, an important part of which is the chemotrigger zone (CTZ). The vomiting centre possesses neurons which are rich in muscarinic cholinergic and histamine containing synapses. These types of neurons are especially involved in transmission from the vestibular apparatus to the vomiting centre. Motion sickness principally involves overstimulation of these pathways due to various sensory stimuli. Hence the action of buclizine which acts to block the histamine receptors in the vomiting centre and thus reduce activity along these pathways. Furthermore since buclizine possesses anti-cholinergic properties as well, the muscarinic receptors are similarly blocked.

TargetActionsOrganism
AHistamine H1 receptor
antagonist
Humans
AMuscarinic acetylcholine receptor M1
antagonist
Humans
Absorption

Rapidly absorbed following oral administration.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Hepatic.

Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Buclizine H1-Antihistamine ActionDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
1,10-PhenanthrolineThe therapeutic efficacy of Buclizine can be decreased when used in combination with 1,10-Phenanthroline.
2,5-Dimethoxy-4-ethylamphetamine2,5-Dimethoxy-4-ethylamphetamine may decrease the sedative and stimulatory activities of Buclizine.
2,5-Dimethoxy-4-ethylthioamphetamine2,5-Dimethoxy-4-ethylthioamphetamine may decrease the sedative and stimulatory activities of Buclizine.
4-Bromo-2,5-dimethoxyamphetamine4-Bromo-2,5-dimethoxyamphetamine may decrease the sedative and stimulatory activities of Buclizine.
4-Methoxyamphetamine4-Methoxyamphetamine may increase the central nervous system depressant (CNS depressant) activities of Buclizine.
5-methoxy-N,N-dimethyltryptamine5-methoxy-N,N-dimethyltryptamine may increase the central nervous system depressant (CNS depressant) activities of Buclizine.
7-Nitroindazole7-Nitroindazole may increase the central nervous system depressant (CNS depressant) activities of Buclizine.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline may increase the central nervous system depressant (CNS depressant) activities of Buclizine.
AbediterolThe risk or severity of Tachycardia can be increased when Buclizine is combined with Abediterol.
AbexinostatThe risk or severity of QTc prolongation can be increased when Buclizine is combined with Abexinostat.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
Not Available

References

General References
  1. Babu TA: Buclizine is back again! This time as a pediatric appetite stimulant. Indian J Pharmacol. 2011 Apr;43(2):219. doi: 10.4103/0253-7613.77383. [PubMed:21572667]
  2. Adam EI: A treatment for the acute migraine attack. J Int Med Res. 1987 Mar-Apr;15(2):71-5. doi: 10.1177/030006058701500202. [PubMed:3556262]
  3. DURHAM MP: Clinical trial of buclizine hydrochloride for vomiting of pregnancy. Br Med J. 1956 Dec 1;2(5004):1276-7. doi: 10.1136/bmj.2.5004.1276. [PubMed:13374321]
  4. FDA approval: Buclizine [Link]
  5. HMDB: Buclizine [Link]
External Links
Human Metabolome Database
HMDB0014498
KEGG Drug
D07547
KEGG Compound
C07777
PubChem Compound
6729
PubChem Substance
46507608
ChemSpider
6473
ChEBI
3205
ChEMBL
CHEMBL1201271
Therapeutic Targets Database
DAP001076
PharmGKB
PA164748223
Wikipedia
Buclizine
ATC Codes
R06AE51 — Buclizine, combinationsR06AE01 — Buclizine

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
  • Stuart pharmaceuticals div ici americas
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
PropertyValueSource
boiling point (°C)218 °CNot Available
logP7.1Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.000246 mg/mLALOGPS
logP6.16ALOGPS
logP7.42ChemAxon
logS-6.2ALOGPS
pKa (Strongest Basic)8.04ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area6.48 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity133.02 m3·mol-1ChemAxon
Polarizability50.93 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9298
Blood Brain Barrier+0.9382
Caco-2 permeable+0.6056
P-glycoprotein substrateSubstrate0.8092
P-glycoprotein inhibitor IInhibitor0.9051
P-glycoprotein inhibitor IINon-inhibitor0.5415
Renal organic cation transporterInhibitor0.6819
CYP450 2C9 substrateNon-substrate0.8508
CYP450 2D6 substrateNon-substrate0.6699
CYP450 3A4 substrateSubstrate0.5976
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.9502
CYP450 2D6 inhibitorNon-inhibitor0.7104
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.5546
Ames testNon AMES toxic0.8885
CarcinogenicityNon-carcinogens0.8723
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.5190 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7081
hERG inhibition (predictor II)Inhibitor0.8779
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - EI-BGC-MSsplash10-014j-4930000000-3910923ac39cbf7127f8
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as diphenylmethanes. These are compounds containing a diphenylmethane moiety, which consists of a methane wherein two hydrogen atoms are replaced by two phenyl groups.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Diphenylmethanes
Direct Parent
Diphenylmethanes
Alternative Parents
Phenylpropanes / Phenylmethylamines / Benzylamines / N-alkylpiperazines / Chlorobenzenes / Aralkylamines / Aryl chlorides / Trialkylamines / Azacyclic compounds / Organopnictogen compounds
show 2 more
Substituents
Diphenylmethane / Phenylpropane / Benzylamine / Phenylmethylamine / Chlorobenzene / Halobenzene / Aralkylamine / N-alkylpiperazine / Aryl chloride / Aryl halide
show 14 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
monochlorobenzenes, N-alkylpiperazine (CHEBI:3205)

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Histamine receptor activity
Specific Function
In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamin...
Gene Name
HRH1
Uniprot ID
P35367
Uniprot Name
Histamine H1 receptor
Molecular Weight
55783.61 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Phosphatidylinositol phospholipase c activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM1
Uniprot ID
P11229
Uniprot Name
Muscarinic acetylcholine receptor M1
Molecular Weight
51420.375 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]

Drug created on June 13, 2005 07:24 / Updated on December 02, 2019 05:22