Serotonin/noradrenaline reuptake

MAOI non-selective monoamine oxidase (A/B) inhibitors RIMA reversible inhibitor of monamine oxidase type A SSRI selective serotonin (5-HT) reuptake inhibitors SNRI serotonin/noradrenaline reuptake inhibitor SNARI selective noradrenaline (NA) reuptake inhibitor NA = 5-HT — DA potency of the drug is very similar in raising the level of both (or all three) monamines NA > 5-HT more selective for NA 5-HT>NA more selective for 5-HT NA increases the release of NA. 

These types of antidepressant were introduced around 10 years after the SSRIs. They include the serotonin noradrenaline reuptake inhibitor venlafaxine and the selective noradrenaline reuptake inhibitor reboxetine. Although there are fewer data about these drugs, clinical experience has shown they are well tolerated and, unlike the SSRIs, they are only weak inhibitors of drug metabolism (Kent, 2000). Depression is a common psychiatric disorder seen in the elderly and often remains untreated or inadequately treated (Forsell and Fastbom, 2000). Venlafaxine was shown to improve the mood in a group of 36 older patients without any effect on cognitive function, an important consideration where there is the possibility of the coexistence of mild or undiagnosed dementia (Tsolaki et al., 2000). 

The most commonly used therapies for anxiety and depression are selective serotonin reuptake inhibitors (SSRIs) and the more recently developed serotonin noradrenaline reuptake inhibitors (SNRIs). SSRIs, which constitute 60% of the worldwide antidepressant and antianxiety market, are frequently associated with sexual dysfunction, appetite disturbances and sleep disorders. Because SSRIs and SNRIs increase 5-HT levels in the brain, they can indirectly stimulate all 14 serotonergic receptor subtypes [2,3], some of which are believed to lead to adverse side effects associated with these drugs. Common drugs for short-term relief of GAD are benzodiazepines. These sedating agents are controlled substances with addictive properties and can be lethal when used in combination with alcohol. The use of benzodiazepines is associated with addiction, dependency and cognitive impairment. 

Many antidepressant drugs have pronounced effects on sleep. Several tricyclic compounds (amitriptyline and others) have sedative actions while others (imipramine and others) are less sedative or even stimulant. Monoamine oxidase inhibitors (MAOIs) have central stimulant effects and may cause insomnia. Specific serotonin reuptake inhibitors (SSRls) and combined serotonin, noradrenaline reuptake inhibitors (SNRIs) can also cause insomnia. 

Venlafaxine and milnacipran are two members of a new class of antidepressants that have selective effects on the reuptake of both serotonin and noradrenaline—serotonin noradrenaline reuptake inhibitors (SNRIs). In theory, based on the findings of B. M. Baron and colleagues [1988 and of J. C. Nelson and colleagues (1991), the combination of these two pharmacological actions should be associated with superior efficacy either in terms of rapid onset of action or extra efficacy at the end of treatment. 

Another approach to correct neurotransmission is to inhibit the reuptake of the neurotransmitters into their presvnaptic endings. If the presynaptic reuptake mechanism of a neurotransmitter is blocked then more of the neurotransmitter will stay in the synaptic cleft and be functionally available. Many antidepressant drugs, called reuptake inhibitors , are thought to act via this mechanism. If selective for serotonin they are called selective serotonin reuptake inhibitors (SSRIs, Chapter 1), but if selective for both serotonin and noradrenaline they are called serotonin noradrenaline reuptake inhibitors (SNRIs). Most older antidepressants, such as the tricyclic compounds amitriptyline, imipramine and clomipramine, have little specificity for any of the neurotransmitters fluoxetine, paroxetine, citalopram and a few others are specific for serotonin venlafaxine is a representative of the SNRIs. A more recent mixed-uptake inhibitor is mirtazepine, and some similar compounds are about to be launched. 

There has been limited short-term experience as anti-obesity agents with the SSRI citalopram [101,102], and with the serotonin-noradrenaline reuptake inhibitor venlafaxine [103], and no recommendations can be made re use of these agents solely as anti-obesity therapy in clinical practice. 

Delgado, P. 2006. Serotonin noradrenaline reuptake inhibitors New hope for the treatment of chronic pain. Int. J. Psych. Cl. Pr., 10(2), 16-21. 

Venlafaxine 10 is a serotonin-noradrenaline reuptake inhibitor used in the treatment of depression. Several sila analogues of venlafaxine have been prepared the silacyclohexylderivative 11 (04WOP200494436), its desmethoxy derivative 12 (06JOM(691)3589) and silacyclopentyl... 

G Ligands of the l,4 -Silaspiro[tetralin-l,4 -piperidine] Type and the Serotonin/Noradrenaline Reuptake Inhibitor Sila-venlafaxine Studies on C/Si Bioisosterism... 

Elafax Venlafaxina Venlafaxine Venlafaxinum Venla-fexine, A serotonin noradrenaline reuptake inhibitor. Used as an antidepressant. Crystals mp n102-104° [(-)-fbrm)] [a]8 -27.1" (c = 1.04 in 95% EtOH) [W-fbrm] [a]85= f27.6 (c = 1.07 in 95% EtOH). Am. Home Products Wyetti-Ayerst Labs. 

Summary Novel potential o ligands of the 1,4 -silaspiro[tetralin-1,4-piperidine] type (compounds lb - 4b, isolated as hydrochlorides) and rac-sila-venlafaxine (rac-5b, a silicon analog of the serotonin/noradrenaline reuptake inhibitor rac-venlafaxine (rac-Sa)) were synthesized. In addition, the sila-venlafaxine enantiomers (R)-5b and (S)-5b and the sila-venlafaxine derivatives rac-6 HCl and ruc-T HCl were prepared. Compounds 3b-HCl and rac-5b-HCl were structurally characterized by single-crystal X-ray diffraction, and rac-5a, rac-Sb, rac-6, and rac-7 were pharmacologically characterized. 

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