Imipramine synthesis

Tricyclic Antidepressants. Imipramine [50-49-7] (32), which was the first tricycHc antidepressant to be developed, is one of many useful psychoactive compounds derived from systematic molecular modifications of the antihistamine prometha2ine [60-87-7] (see Histamine and histamine antagonists). The sulfur atom of prometha2ine was replaced with an ethylene bridge and the dimethylamino group attached to an / -propyl group, rather than to an isopropyl one, of the side chain. The actual synthesis of (32) is typical of the compounds in this class (37). 

Besson, M. J., Cheramy, A., and Glowinski, J. (1969) Effects of amphetamine and desmethyl-imipramine on amine synthesis and release in central catecholamine containing neurons. Eur. J. Pharmacol., 7 111-114. 

Imidazolone synthesis, 291 Imidoline, 259 Imipramine, 420 Indapamide, 349 Indazole synthesis, 350 Indoles, as starting material for benzodiazepines, 405 Indomethacin, 345 Indoramin, 344 Incfoxoie, 254, 340 Inflammation, 63 Influenza A, 18 Inhibition,... 

Desipramine Desipramine, 10,1 l-dihydro-5-[3-(methylamino)propyl]-5H-dibenz[b,f] azepine (7.1.13), differs from imipramine in that it contains only one methyl group on the nitrogen atom of the propylamine side chain. The suggested methods of desipramine synthesis are very simple, and the difference lies only in the manner in which the secondary methylamine group is introduced into the structure of the drug. 

Finally, a third way of synthesis is from imipramine (7.1.1), which nndergoes demethylation by snccessive reaction with ethyl chloroformate, giving 5-[3-(Af-carbethoxy-iV-methyl)aniino-propyl]-10,ll-dihydro-5H-dibenz[b,f azepine (7.1.15), the alkaline hydrolysis of which leads to desipramine (7.1.13) [23,24],... 

Nalepa I, Kreiner G, Kowalska M, Sanak M, Zelek-Molik A, Vetulani J (2002) Repeated imipramine electroconvulsive shock increase alpha(lA)-adrenoceptor mRNA level in rat prefrontal cortex. Eur J Clin Pharmacol 444 151-159 Nesse RM, Ciu-tis GC, Thyer BA, McCann DS, Huber-Smith MJ, Knopf RF (1985) Endocrine and cardiovascular responses during phobic anxiety. Psychosom Med 47 320-332 Nisenbaiun LK, Zigmund MJ, Sved AF, Abercrombie ED (1991) Prior exposure to chronic stress results in enhanced synthesis and release of hippocampal norepinephrine in response to a novel stressor. J Neurosci 11 1473-1484 Nutt DJ (1989) Altered alpha2-adrenoceptor sensitivity in panic disorder. Arch Gen Psychiatry 46 165-169... 

Shopsin B, Gershon S, Goldstein M, et al. Use of synthesis inhibitors in defining a role for biogenic amines during imipramine treatment in depressed patients. Psychopharmacoi Commun 1975 1 239-249. 

The synthesis of 614, a conformationally rigid analogue of the tricylic antidepressant imipramine, also begins with an A,A-diisopropyl nicotinamide ortho metalation (Scheme 181) [87H(26)3165]. Thus, LiTMP depro-... 

Other recent reports which indirectly tend to weaken the concept that norepinephrine is the sole alerting neurohumor indicate that (1) imipramine hyperactivity may result from blocking uptake and reducing nervous impulse flow in central serotonin neurons (2) drugs which Inhibit uptake of catecholamines also block serotonin accumulation in rabbit brain stem preparations (3) the increase in overt stimulation caused by 5-hydroxy-tryptophan may be associated with Impaired norepinephrine synthesis rather than increased norepinephrine release and (4) norepinephrine and dopamine inhibit electrical activity of central neurons as determined microelectro-phoretically although another study indicated that norepinephrine does cause neuronal excitation ... 

Imipramine blocked the uptake of dopamine at central aminergic neurons in the rat Lithium inhibited the electrically-induced release of NE and 5" in brain slices 3 and did not interfere with the transfer rate of Ma from blood to brain tissue. Data were reported which suggested that the therapeutic effect of electroshock treatment may be due to increased levels of brain amines 5 or to an increase in NE turnover rate . In a study of catecholamine turnover rates in mouse brain it was found that neuroleptics have a predominant influence on dopamine metabolism while antidepressants selectively affect NE metabolism, a higher rate of NE synthesis was found in the forebrain of "mouse-killing" rats over that of controls Imipramine blocked the muricidal behaviour9 and also lowered NE turnover . 

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