Clomipramine

SSRIs are well tolerated. Adverse effects for compounds in this class include nervousness, tremor, dizziness, headache, insomnia, sexual dysfunction, nausea, and diarrhea. In addition, the tricycHc antidepressant clomipramine (33), which is a potent nonselective serotonin reuptake inhibitor, is approved for treatment of obsessive—compulsive disorder. 

Doxepin [1668-19-5] (38), unlike other commercially available tricyclics, has an oxygen atom in the bridge between the two aromatic rings. It is marketed as a cis—trans mixture (1 5) of isomers, both of which are active. This close relative of amitriptyline (33) has both sedative and anxiolytic properties associated with its antidepressant profile. Maprotiline [10262-69-8] (39) and amoxapine [14028-44-5] (40) are pharmacologically, although not chemically, similar to the tricycHc secondary amines. Clomipramine [303-49-1] (41) has similar pharmacological and antidepressant efficacy. However, clomipramine is approved by the U.S. FDA only for the treatment of obsessive—compulsive disorder. Representative brands of tricycHc antidepressants marketed in the United States are Hsted in Table 2. 

Amitriptylin oxide 3-(Dimethylamino) propyl chloride Amitriptyline HCI Ch/orprothixene Clomipramine Cyclobenzaprine Imipramine HCI Oxetorone fumarate Prothipendyl HCI... 

Antidepressants are used in the treatment of neuropathic pain and headache. They include the classic tricyclic compounds and are divided into nonselective nor-adrenaline/5-HT reuptake inhibitors (e.g., amitriptyline, imipramine, clomipramine, venlafaxine), preferential noradrenaline reuptake inhibitors (e.g., desipramine, nortriptyline) and selective 5-HT reuptake inhibitors (e.g., citalopram, paroxetine, fluoxetine). The reuptake block leads to a stimulation of endogenous monoaminer-gic pain inhibition in the spinal cord and brain. In addition, tricyclics have NMDA receptor antagonist, endogenous opioid enhancing, Na+ channel blocking, and K+ channel opening effects which can suppress peripheral and central sensitization. Block of cardiac ion channels by tricyclics can lead to life-threatening arrhythmias. The selective 5-HT transporter inhibitors have a different side effect profile and are safer in cases of overdose [3]. 

Sedation and dry mouth are the most common adverse reactions seen with the use of TCAs. Tolerance to these effects develops with continued use. Orthostatic hypotension can occur with the administration of the TCAs. Orthostatic hypotension is a drop in blood pressure of 20 to 30 points when a person changes position, such as going from a lying position to a standing position. Mental confusion, lethargy, disorientation, rash, nausea, vomiting, constipation, urinary retention, visual disturbances, photosensitivity, and nasal congestion also may be seen. Sexual dysfunction may occur with administration of clomipramine. 

Remember that a high incidence of sexual dysfunction is associated with clomipramine therapy. 

C15HHCI2NO 92428-58-5) see Clomipramine 3-chloro-10,ll-dihydro-5H-dibenz[i4/]azepine-5-carb-oxylic acid 3-(dimethylamino)propyl ester (C20H23CIN2O2 94758-20-0) see Clomipramine... 

C5H12CIN 109-54-6) see Acepromazine Bencyclane Benzydamine Chlorpromazine Citalopram Clomipramine Dimetacrine Imipramine Promazine Prothipendyl Triflupromazine... 

Fig 1 Chromatogram of imipramine and phenothiazine derivatives after staining with Forrest reagent [4] 1 = imipramine, 2 = desipramine, 3 = clomipramine, 4 = lofepramine, 5 = trimipramine, 6 = thioridazine, 7 = chlorphenethazine, 8 = periciazine, 9 = promazine, 10 = promethazine. 

Edge blue. clomipramine imiprainine lofepramine trimipramine ... 

Citrinine la 69,147,148 Citronellal la 158,159 CitroneUol la 68-70,327 Citronellyl acetate la 68 Claisen-Tischenko reaction 15 54 Clathrate complex 15 303 Clavin alkaloids 15 243 Clavine alkaloids 15 246,252 Cleanup la 119 Clemastin 15 354 Clenbuterol 15 106,107,354 Clobutinol 15 354 Cloforex 15 194,296 Clomethiazole lb 354 Clomipramine 15 352,354,355 Clonacillin lb 301 Clonidine 15 354 Clopamide 15 354 Clorexolon 15321 Clotrimazol 15 98,99,401,402 Cloxacillin 1584,188 Clozapin 15 354 Cnicin 15 290... 

Decision analytic models have been constmcted to compare the costs of TCAs with those of SSRIs and other compounds. These comparisons have included imipramine or amitriptyline versus paroxetine or sertraline (Stewart, 1994) imipramine versus paroxetine Qonsson and Bebbington, 1994 McFarland, 1994 Lapierre et al, 1995) fluoxetine versus amitriptyline, clomipramine, doxepin and imipramine (Le Pen et al, 1994) venlafaxine versus amitriptyline, desipramine. 

All TCAs are either secondary- or tertiary-amines of a dibenzazepine nucleus (Fig. 20.3), and they all inhibit neuronal reuptake of noradrenaline and/or 5-HT but are much less potent as dopamine reuptake blockers. A common claim is that secondary amines (e.g. desipramine) are preferential inhibitors of noradrenaline uptake whereas the tertiary derivatives (e.g. imipramine, doxepin and amitryptyline) preferentially inhibit 5-HT uptake. However, when Richelson and Pfenning (1984) actually compared the effects of a wide range of antidepressants on the synaptosomal uptake of [ H]monoamines in vitro, and compared their A s, instead of merely ranking /C50S collected from different studies, they found that tertiary- and secondary-substituted compounds were equi-potent inhibitors of [ H]noradrenaline uptake. Moreover, all the TCAs turned out to be more potent inhibitors of [ H]noradrenaline than of [ H]5-HT uptake. Tertiary amines are even less convincing inhibitors of 5-HT reuptake in vivo, because any such action is diminished by their metabolism to secondary amines (e.g. imipramine to desipramine amitriptyline to nortriptyline). Only clomipramine retains any appreciable 5-HT uptake blocking activity in vivo with (an unimpressive) five-fold selectivity for 5-HT versus noradrenaline. 

Allopurinol, aspirin, carbamazepine, chlorpropamide, clomipramine, clozapine, colchicine, desipramine, gold salts, imipramine, levodopa, penicillamine, phenothiazines, phenytoin, propylthiouracil, and sulfonylureas... 

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