First generation tricyclic

The precise mechanism by which the first-generation tricyclic antidepressants, monoamine oxidase inhibitors, and the newer-generation antidepressants exert their effects is uncertain. However, it is clear that antidepressants exert their effects at both pre- and postsynaptic receptor sites (Figure 43.3 and Figure 43.4). 

The first-generation tricyclic antidepressants, the monoamine oxidase inhibitors, and the newer agents can cause sedation, insomnia, orthostatic hypotension, or nausea. Because of their anticholinergic properties, they may also produce cardiac toxicides (Table 43.2). 

The first-generation tricyclic antidepressants, the monoamine oxidase inhibitors, and the newer agents can... 

SAR of Loratadine. The drug is intimately related to the first generation tricyclic antihistaminics and also to the antidepressants. 

Since their introduction in the 1980s, selective serotonin reuptake inhibitors (SSRls) such as paroxetine, fluoxetine, and citalopram have enjoyed tremendous clinical and commercial success due to their improved safety profile when compared with first-generation tricyclic antidepressants like imipramine. Nevertheless, they still display several side effects including gastrointestinal distress, anxiety, insomnia, weight gain, and sexual dysfunction. Like other current antidepressants. 

Cyclobenzaprine is a central-acting muscle relaxant that is commonly used to treat pain from injury, muscle spasms, and other painful musculoskeletal conditions. It is structurally related to first-generation tricyclic antidepressants such as imipramine and amitriptyline and appears to inhibit the uptake of norepinephrine in the locus coeruleus. Tricyclic compounds with norepinephrine reuptake-inhibiting properties have been shown to exert analgesic effects in chronic nerve and muscle pain by acting primarily within the central nervous system at brainstem as opposed to spinal cord levels, although their action on the latter may contribute to their overall skeletal muscle relaxant activity. The exact mechanism of action of cyclobenzaprine is unknown. 

Another example of an efficient domino RCM is the synthesis of the highly functionalized tricyclic ring system 6/3-72 by Hanna and coworkers [252], which is the core structure of the diterpene guanacastepene A (6/3-73) (Scheme 6/3.21) [253]. Reaction of 6/3-71 in the presence of 10 mol% of Grubbs II catalyst 6/3-15 led to 6/3-372 in 93 % yield. Interestingly, the first-generation Ru-catalyst 6/3-13 did not allow any transformation. 

Tricyclic antidepressant A family of first-generation (typical) antidepressants with a three-ringed structure that inhibit the action of monoamine transporters. 

Tricyclic antidepressants (TCAs) first-generation antidepressants... 

Pharmacokinetic studies of 63a and 65a in mice demonstrated that the compounds had modest bioavailability (21% and 13%, respectively) but short plasma half-lives (tm <10 min).80 While pharmacokinetic parameters in other species have not been reported, it seems likely that issues relating to the absorption, distribution, metabolism, and excretion of this first generation of tricyclic inhibitors needs to be... 

Tricyclic antidepressants (TCAs) - first-generation antidepressants Examples - tertiary amine type imipramine, amitriptyline, dothiepin, clomipramine... 

The potentiation of sedative effects from benzodiazepines when combined with centrally acting drugs with antihistamine properties (for example first-generation antihistamines, tricyclic antidepressants, and neuroleptic drugs) can pose problems (143). Antihistamines that do not have central actions do not interact with benzodiazepines as in the case of mizolastine and lorazepam (144), ebastine and diazepam (145), and terfenadine and diazepam (143). 

Serotonin-Selective Reuptake Inhibitors. Since their introduction in the mid-1980s SSRIs have become the most widely used of all antidepressants. This is largely because of their improved safety and tolerability in clinical use. Although the SSRIs are no more efficacious or rapid in onset of action than the tricyclics, they lack most of the serious toxicity and adverse side effects associated with the first-generation drugs. The relative absence of cardiac toxicity makes the SSRIs relatively safe in overdose (36). Fatal overdose... 

The effects of cholinesterase inhibitors may be reduced by first-generation antihistamine medications, tricyclic antidepressants, and antipsychotics, and the client should not take these medications simultaneously. The nurse should ask the elient about other medications taken. 

Tricyclic first generation antidepressants as for example imipramine and dothiepin (fig. 2) not only inhibit 5-HT and NE reuptake but also act as antagonists on histamine-1, cholinergic muscarine, adrenergic alpha and 5-HT2 receptors [26-28]. 

Coupling an ROM event with enyne metathesis opens up further possibilities for RRM. As already discussed for reactions involving only olefins, norbomenes are valuable strained cycloolefins for the ring-opening step [22], Treatment of the norbomene derivative 123 with the first-generation Grubbs catalyst 1 under ethylene atmosphere induced a smooth domino ROM/enyne RCM/diene RCM process with quantitative formation of the tricyclic compound 124 (Scheme 2.45) [22b]. 

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