General
Preferred name
pizotifen
Synonyms
PIZOTYLINE MALATE ()
Pizotifene ()
PIZOTYLINE ()
BC-105 ()
Pizotyline (malate) ()
BC-105 (malate) ()
Pizotifen Malate ()
Pizotyline (malate)BC-105 (malate)BC-105 ()
Pizotifen (malate) ()
Sandomigran, pizotyline,BC-105 ()
Pizotyline, BC-105 ()
Sandomigran ()
Pizotifen ()
P&D ID
PD012413
CAS
15574-96-6
24359-22-6
5189-11-7
Tags
natural product
drug
available
Drug Status
approved
Drug indication
Headache
Anabolic
Serotonin Inhibitor (specific in migraine)
Antidepressant
Probe control
Probe control not defined
Orthogonal probes
0
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
PHARMACODYNAMICS
Various studies have shown pizotifen to be effective in the prophylaxis of migraines in reducing the frequency and severity of vascular headaches [A32536]. Evidence from studies _in vivo_ and _in vitro_ demonstrate antagonistic actions towards serotonin and histamine. Pizotifen blocks the postsynaptic 5-HT2 receptors, as supported by antagonism of several direct agonists of 5-HT receptors [A32538]. It is an antagonist at histamine H1 receptors, and is weakly anticholinergic [A32550]. It also binds to α1- and α2-adrenergic receptors, and dopamine receptors [A32550]. Pizotifen elicits a minimal effect as an epinephrine or bradykinin antagonist [L2292]. Pizotifen exhibits weak sedative properties in mouse and monkey studies, as indicated by inhibition of locomotion and potentiation of barbiturates, without changes in cardiac or respiratory rates [L2292]. In dogs, intravenous administration of pizotifen cause rapid hypotension but was reversed to normal within 30 minutes [L2292]. Pizotifen was shown to inhibit serotonin uptake in the isolated perfused cat spleen and, _in vivo_, inhibits serotonin-induced contractions in rat uterus and cat nictiating membrane [A32533]. In contrast, pizotifen demonstrated a venoconstrictor activity _in vivo_ when orally or intravenously administered to saphenous veins in conscious dogs [A32537]. Pizotifen has the potential to stimulate the appetite and may cause weight gain upon treatment [A32533]. ; ; In a double-blind clinical study of patients with mild to moderate depression, treatment of pizotifen led to clinical improvement of the depressive symptoms. However, deterioration of the schizophrenic emotional symptoms was also observed in patients with depression and chronic schizophrenia [A32532]. This indicates that pizotifen may potentially improve the symptoms of patients with depressions in conjunction with migraines [A32532]. ; ; Neuroprotective effect of pizotifen was investigated _in vitro_ in a mouse cell model of Huntington's disease (HD). According to a chemical screen of a mouse HdhQ111/Q111 striatal cell model of HD, treatment of pizotifen was associated with increased ATP levels and decreased activation of caspase-3, leading to enhanced cell viability [A32539]. Transient activation of ERK signalling pathway lasting for less than 3 hours was also observed. In the R6/2 transgenic mouse model of HD, rotarod performance of the mouse treated with pizotifen was seen, accompanied by an increase in DARPP-32 protein expression and restoration of striatal area [A32539]. However these effects being reflected _in vivo_ are not established.
DESCRIPTION
Pizotifen is a benzocycloheptene-based anti-migraine drug, acting principally as an antagonist of serotonin 5-HT2A and 5-HT2C receptors.
(GtoPdb)
TOXICITY
The oral Lowest published toxic dose (TDLo) is 12.86 mg/kg in man [MSDS]. Oral LD50 ranges from 410 to 1500 mg/kg in rat [MSDS, L2292]. Oral LD50 in mouse and rabbit is 880 mg/kg and 700 mg/kg, respectively [L2292]. The LD50 following intravenous administration in rat was 17 mg/kg [L2292].; ; In adults, the symptoms of overdosage include sedation, drowsiness (preceding excitement, convulsions, and postictal depression), dizziness, hypotension, dryness of the mouth, confusion, tachycardia, ataxia, nausea, vomiting, dyspnea, cyanosis, convulsions, coma, respiratory paralysis and CNS depression [L2292]. Antihistamine toxicity of pizotifen in children may involve excitation, hallucinations, ataxia, incoordination, convulsions, fixed dilated pupils, flushed faces, and fever, leading to coma and cardiorespiratory collapse [L2292]. The use of activated charcoal is recommended in the management of overdose. For drug recent uptake, induction of emesis or gastric lavage and diuresis should be performed [L2292]. Supportive measures should be initiated to maintain effective respiration while closely monitoring vital signs. While severe hypotension must be corrected, the use of adrenaline may produce paradoxical effects [L2292]. ; ; As pizotifen has the potential to cause tachycardia, an ECG should be performed and attention directed at the QRS and QT intervals [L2292]. Excitatory states or convulsions induced by pizotifen may be treated with short-acting barbiturates or benzodiazepines. However analeptics should be avoided [L2292].
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Cell lines
0
Organisms
3
Compound Sets
22
AdooQ Bioactive Compound Library
Cayman Chemical Bioactives
ChEMBL Drugs
Drug Repurposing Hub
DrugBank
DrugBank Approved Drugs
DrugCentral
DrugCentral Approved Drugs
DrugMAP
DrugMAP Approved Drugs
DrugMatrix
Guide to Pharmacology
Ki Database
NIH Clinical Collections (NCC)
NPC Screening Collection
Other bioactive compounds
Prestwick Chemical Library
ReFrame library
Selleckchem Bioactive Compound Library
The Spectrum Collection
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
62
Molecular Weight
295.14
Hydrogen Bond Acceptors
2
Hydrogen Bond Donors
0
Rotatable Bonds
0
Ring Count
4
Aromatic Ring Count
2
cLogP
4.37
TPSA
3.24
Fraction CSP3
0.37
Chiral centers
0.0
Largest ring
7.0
QED
0.7
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Pathway
GPCR/G protein
Neuroscience
Neuronal Signaling
Target
5-HT
HTR1A, HTR2A, HTR2C
5-HT Receptor
MOA
5-HT Receptor agonist
serotonin receptor antagonist
Indication
migraine headache
Source data
