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Venlafaxine is a serotonin-norepinephrine reuptake inhibitor (SNRI) with a history dating back to the 1980s, developed by a research team at Wyeth Pharmaceuticals. The discovery of this compound was based on ongoing research into novel antidepressants, aiming to provide a drug with a dual mechanism of action to improve efficacy in patients who do not respond well to traditional selective serotonin reuptake inhibitors (SSRIs). Key chemists and pharmacologists involved in the synthesis and bioactivity evaluation of the compound included John P. Yardley, G. E. Morris Husbands, and Eric A. Muth, among others. Their research ultimately led to the development of venlafaxine, a compound that demonstrated effective inhibition of serotonin and norepinephrine transporters in in vitro experiments.An immediate-release formulation of venlafaxine (IR), marketed as Effexor, was approved by the U.S. Food and Drug Administration (FDA) in 1993 for the treatment of major depressive disorder. This marked the first clinical application of an SNRI antidepressant. Subsequently, in order to improve patient compliance and reduce the side effects caused by peak drug concentration, Wyeth continued to develop an extended-release formulation (ER), marketed as Effexor XR, which was approved by the FDA in 1997. The launch of Effexor XR further solidified venlafaxine's position in the treatment of depression. Over time, the indications for venlafaxine have also expanded to include generalized anxiety disorder, social anxiety disorder, and panic disorder.
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A optically active version of Venlafaxine, a selective serotonin noradrenaline reuptake inhibitor. Used as an antidepressant
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ChEBI: A tertiary amino compound that is N,N-dimethylethanamine substituted at position 1 by a 1-hydroxycyclohexyl and 4-methoxyphenyl group.
Biological Functions
Venlafaxine (Effexor) inhibits the reuptake of both
serotonin and norepinephrine at their respective presynaptic
sites.This drug does not have significant effects at
muscarinic, histamine, or α-adrenergic receptors and
therefore is devoid of many of the side effects associated
with the TCAs.Venlafaxine and its active metabolite O-desmethyl-venlafaxine, have half lives of 5 and
11 hours respectively, so dosing twice a day is necessary.
However, an extended release preparation (Effexor
XR) now allows for once-daily dosing and better tolerance.
Venlafaxine has a side effect profile similar to that
of the SSRIs. Higher doses of venlafaxine
result in modest increases in blood pressure in approximately
5% of patients.Venlafaxine has minimal effects
on the cytochrome P450 enzyme system.
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The structure and activity of venlafaxine (Effexor) are in accordwith the general SARs for the group. As expected, it isan effective antidepressant. Venlafaxine is a serotonin–norepinephrinereuptake inhibitor (SNRI).
Pharmaceutical Applications
Venlafaxine is a serotonin and noradrenalin reuptake inhibitor (SNRI) and is used as an antidepressant. Compared to tricyclic antidepressants, it lacks the antimuscarinic and sedative side effects. Nevertheless, treatment with venlafaxine can lead to a higher risk of withdrawal symptoms.
Clinical Use
Venlafaxine is a methoxyphenylethylamine antidepressant that resembles an open TCA with one of the
aromatic rings replaced by a cyclohexanol ring and a dimethylaminomethyl group rather than a
dimethylaminopropyl chain.
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The potential for cardiotoxicity with venlafaxine during normal use and for various toxicities in overdose
situations are key concerns. Venlafaxine displays minimal in vitro affinity for the other neural neurotransmitter
receptors and, thus, a low probability for adverse effects. To minimize GI upset (e.g., nausea), venlafaxine
can be taken with food without affecting its GI absorption. Venlafaxine should be administered as a single
daily dose with food at approximately the same time each day. The extended-release capsules should be
swallowed whole with fluid and should not be divided, crushed, chewed, or placed in water.
Whenever venlafaxine is being discontinued after more than 1 week of therapy, it generally is recommended
that the patient be closely monitored and the dosage of the drug be tapered gradually to reduce the risk of
withdrawal symptoms.
Although venlafaxine is a weak inhibitor of CYP2D6, variability has been observed in the pharmacokinetic
parameters of venlafaxine in patients with hepatic or renal function impairment. As a precaution, elderly
patients taking venlafaxine concurrently with a drug that has a narrow therapeutic index and also is
metabolized by CYP2D6 should be carefully monitored. Concurrent use of CYP3A4 inhibitors with venlafaxine
has been shown to interfere with its metabolism and clearance. Similar to the other antidepressants that block
5-HT reuptake, venlafaxine may interact pharmacodynamically to cause toxic levels of 5-HT to accumulate,
leading to the 5-HT syndrome.
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