| Company Name: |
AKASH PHARMA EXPORTS
|
| Tel: |
+91-9388123451 +91-9846039283 |
| Email: |
akashpharmaexports@gmail.com |
| Products Intro: |
Product Name:Doxepin
Purity:99% Package:1kg,5 kg, 10 kg,25kg and 1 MT
|
| Company Name: |
SynZeal Research Pvt Ltd
|
| Tel: |
+1 226-802-2078 |
| Email: |
standards@synzeal.com |
| Products Intro: |
Product Name:Doxepin
|
|
| | DOXEPIN Basic information |
| Product Name: | DOXEPIN | | Synonyms: | CIS,TRANS-DOXEPIN;DOXEPIN | | CAS: | | | MF: | C19H21NO | | MW: | 0 | | EINECS: | | | Product Categories: | | | Mol File: | Mol File |  |
| | DOXEPIN Chemical Properties |
| pka | pKa 8.0 (Uncertain) | | BCS Class | 1 |
| | DOXEPIN Usage And Synthesis |
| Uses | The mechanism of action of doxepin is presumable linked to the effect on the adrenergic
transmission in the CNS, in particular to the blockage of neuronal norepinephrine uptake.
Doxepin is used in anxious-depressive and anxious conditions, neuroses, alcoholism,
organic illnesses of the CNS, and psychoses. | | Indications | The tricyclic tertiary amine doxepin (Zonalon, Prudox),
a potent H1- and H2-receptor antagonist, is indicated for
the short-term relief of pruritus associated with topical
eczematous dermatitis. Systemic absorption occurs, and
the drug may potentiate or alter the metabolism of a va-riety of other systemic agents. Drowsiness is the most
common adverse side effect. | | Mechanism of action | Because doxepin is administered as an 85:15 mixture of geometric isomers, its mechanism of action and
antidepressant properties reflects this ratio. Therefore, dioxepin's selectivity for inhibiting presynaptic NE
reuptake is most likely caused by the 85% presence of the E-isomer in the geometric mixture. Its
antidepressant activity is similar to amitriptyline. Data suggest NE reuptake inhibitory potency comparable to
imipramine and clomipramine; the fact that doxepin is an 85:15 mixture of E- and Z-geometric isomers clouds
its true efficacy for SERT or NET . The formation of N-desmethyldoxepin results in inhibition of NE reuptake
with enhanced noradrenergic activity. As a result of these mixed effects on the 5-HT and NE transporters,
doxepin shares the pharmacological and adverse-effect profile of the other TCAs.
After oral dosing, no significant difference was found between the bioavailability of the E- and Z-isomers. The plasma concentrations of the doxepin isomers remained roughly those of the administered drug, whereas the ratio for the metabolites,
E-N-desmethyldoxepin and Z-N-desmethyldoxepin, were approximately 1:1. This similarity in ratios of
metabolites is attributed to E-doxepine being primarily metabolized in parallel by CYP2D6 and CYP2C19,
whereas Z-doxepine is primarily metabolized only by CYP2C19 and not at all by CYP2D6.
Its Z-N-demethylated metabolite is pharmacologically more active than its E-metabolite as an inhibitor of 5-HT
and NE reuptake. Both isomers of doxepin showed large volumes of distribution and relatively short
half-lives in plasma, suggestive of extensive distribution and/or tissue binding. Renal clearances did not differ
for the isomers. | | Clinical Use | Tricyclic antidepressant | | Side effects | Doxepin (Sinequan, Zonalon) is a combined H1 and H2 receptor antagonist. It is
also a tricyclic antidepressant with antianxiolytic effects. Adverse side effects include
sedation and anticholinergic symptoms, in addition to tachycardia, hypotension,
and prolongation of the PR and QRS intervals on electrocardiogram. Side effects
are usually mild and may include burning, stinging, drowsiness, and dry mouth.
The incidence of side effects increases when applied to more than 10% of the body
surface area or when duration of therapy exceeds 8 days. Cases of acute contact
dermatitis to topical Zonalon have been reported. | | Synthesis | Doxepin, (11[16H]-(3-dimethylaminopropyliden)-6,11-dihydrobenz[b,e] oxepine)
(7.1.11), is synthesized in an analogous manner by reacting 6,11-dihydrodibenz-[b,e]oxepin-
11-one (7.1.9) with 3-dimethylaminopropylmagnesium bromide and the subsequent dehydration of the resulting tertiary alcohol (7.1.10) by hydrochloric acid [14–17]. 
The initial 6,11-dihydrodibenz[b,e]oxepin-11-one (7.1.9) is synthesized from the ethyl
ester of 2-phenoxymethyl benzoic acid (7.1.7), which is easily synthesized by reacting
ethyl 2-bromomethylbenzoate with phenol in the presence of a base. The resulting ester
(7.1.5) is hydrolyzed into 2-phenoxymethylbenzoic acid (7.1.8), which is cyclized to 6,11-
dihydrodibenz[b,e]oxepin-11-one (7.1.9) by trifluoroacetic acid anhydride.
| | Drug interactions | Potentially hazardous interactions with other drugs
Analgesics: increased risk of CNS toxicity with
tramadol; possibly increased risk of side effects with
nefopam; possibly increased sedative effects with
opioids
Anti-arrhythmics: increased risk of ventricular
arrhythmias with amiodarone - avoid; increased
risk of ventricular arrhythmias with disopyramide,
flecainide or propafenone; avoid with dronedarone.
Antibacterials: increased risk of ventricular
arrhythmias with moxifloxacin and possibly
delamanid and telithromycin - avoid with
moxifloxacin
Anticoagulants: may alter anticoagulant effect of
coumarins.
Antidepressants: enhanced CNS excitation and
hypertension with MAOIs and moclobemide -
avoid; concentration possibly increased with SSRIs;
risk of ventricular arrhythmias with citalopram
and escitalopram - avoid; possible increased risk of
convulsions with vortioxetine.
Antiepileptics: convulsive threshold lowered;
concentration reduced by carbamazepine,
phenobarbital and possibly fosphenytoin, phenytoin
and primidone
Antimalarials: avoid with artemether/lumefantrine
and piperaquine with artenimol.
Antipsychotics: increased risk of ventricular
arrhythmias especially with droperidol, fluphenazine,
haloperidol, pimozide, risperidone, sulpiride and
zuclopenthixol - avoid; increased antimuscarinic
effects with clozapine and phenothiazines;
concentration increased by antipsychotics.
Antivirals: increased risk of ventricular arrhythmias
with saquinavir - avoid; concentration possibly
increased with ritonavir
Atomoxetine: increased risk of ventricular
arrhythmias and possibly convulsions
Beta-blockers: increased risk of ventricular
arrhythmias with sotalol.
Clonidine: tricyclics antagonise hypotensive
effect; increased risk of hypertension on clonidine
withdrawal.
Dapoxetine: possible increased risk of serotonergic
effects - avoid.
Dopaminergics: avoid use with entacapone; CNS
toxicity reported with selegiline and rasagiline.
Pentamidine: increased risk of ventricular
arrhythmias.
Sympathomimetics: increased risk of hypertension
and arrhythmias with adrenaline and noradrenaline;
metabolism possibly inhibited by methylphenidate. | | Metabolism | Approximately 55-87% of doxepin undergoes first
pass metabolism in the liver, forming the primary active
metabolite desmethyldoxepin.
Doxepin is excreted in the urine, mainly in the form of its
metabolites, either free or in conjugated form. | | Dosage forms | Tablets: 10 mg PO q.i.d., may increase dose as tolerated. Zonalon
cream: apply to affected areas t.i.d. to q.i.d. up to 8 days. |
| | DOXEPIN Preparation Products And Raw materials |
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