Imipramine , analog

As with imipramine, it is used for depression of various etiology. In terms of efficacy, it is analogous to imipramine. Surmontil is a synonym of trimipramine. 

The positive effects of the monoamine oxidase inhibitor isoniazid and the amine reuptake blocker imipramine were both discovered by accident. Isoniazid was being used as an antitubercular drug when patients reports of elation led Nathan Kline to test and to demonstrate its antidepressant power. Ronald Kuhn had synthesized imipramine, a tricyclic molecule, as a possible me-too analog of chlorpromazine. When Kuhn found that it had little or no antipsychotic potential, he tried it out on depressives, and voila They got better. After a while, that is. As with isoniazid, imip-ramine s antidepressant action was evident only after one to four weeks of administration. 

The phenothiazines, such as chlorpromazine, used in the treatment of schizophrenia, the tricyclic antidepressant drugs such as imipramine and amitryp-tUine, antimalarials such as quinacrine, and the anticancer agent adriamycin are structural analogs of riboflavin (see Figure 7.6) and inhibit flavokinase. In experimental animals, administration of these drugs at doses equivalent to those used clinically results in an increase in the EGR activation coefficient (Section 7.5.2) and increased urinary excretion of riboflavin, with reduced tissue concentrations of riboflavin phosphate and FAD, despite feeding diets providing more riboflavin than is needed to meet requirements (Pinto et al., 1981). 

Figure 7.6. Drugs that are structural analogs of riboflavin and may cause deficiency. Relative molecular masses (Mr) riboflavin, 376.4 quinacrine, 472.9 (dihydrochloride) chlorpromazine, 318.9 imipramine, 280.4 amitryptyline, 277.4 and adriamycin (doxorubicin), 543.5.

There is one report of the use of the tricyclic antidepressant imipramine hydrochloride to control urospermia in a stallion with detrusor dysfunction and decreased urethral sphincter tone (Oristaglio Turner et al 1995 see Ch. 11). Imipramine is a phe-nothiazine analog and appears to have a adrenergic effects via the blockade of norepinephrine reuptake at nerve terminals. It was administered orally at 0.8 mg/kg to this stallion 2-3 h prior to semen collection and was thought to improve urethral sphincter tone and limit urospermia. However, this improvement was not documented using urethral pressure profilometry and the owner of the stallion was also instructed to collect from the stallion shortly after it was observed to urinate. Consequently, it is not clear whether the imipramine treatment was really of any benefit. 

Tricyclic amine antidepressants (TCAs) are nonselective5-HT and NE reuptake inhibitors. Two TCAs, imipramine (20) and desi-pramine (21), are used to treat bulimia nervosa, primarily as second-line therapies. Imipramine, a tertiary amine, is a 5-HT re-uptake inhibitor with weak NE reuptake activity. Desipramine, a secondary amine and the des-ethyl analog of imipramine, is a NE reuptake inhibitor. Other TCAs used less frequently to treat BN include amitriptyline (22) and its N-desmethyl analog nortripyline (23). 

Replacement of the sulfur atom in promazine by two methylene groups leads to imipramine (XXVI) which is not a tranquilizer, but is instead a clinically useful antidepressant agent (22, 25). Similarly, the dibenzocyclohepta-diene analog, amitriptylene (XXVII) (2), is devoid of tranquilizing activity and is a useful antidepressant like imipramine. 

Imipramine is structurally analogous to chlorpromazine but the replacement of sulphur by a —CHj - CH2— linkage causes a considerable change in steric and electronic geometry and in pharmacological activity. Like the phenothiazine compounds, imipramine shows some activity against acetylcholine, noradrenaline and histamine , and extrapyramidal side effects... 

Like imipramine and dothiepin their substituted analogs clomipramine, danopramine and cyanodothiepin also have a pronounced antagonistic effect on several neiu-otransmitter receptors which may contribute to the overall pharmacological effect or side-effect of the drugs. 

EXP-561 (31) may also be placed in this group. It had an antidepressant profile analogous to imipramine and in some respects (e.g. tetrabenazine... 

Two other groups of drugs encountered in casework samples are the antipsy-chotics and antiinflammatory drugs. The phenothiazines, such as chloropromazine and its analogs, and the tricyclic antidepressants, such as amitriptyline, nortriptyline and imipramine, account for the majority of antipsychotic drugs that are normally detected. The most frequently used procedures for the detection... 

Antidepressive activity was noted for some tricyclic compounds having a six-membered central ring. A series of naphthyrldones, C-29 C-42 ( ). and C- 5 (7c). caused inlpramine—like activity in animals. The Influence of on central biogenic amine levels," as well as its absorption, distribution and excretion, was Investigated in mice and rats. Several phenothiazine derivatives had antidepressive activity. In extensive clinical trials fluoracizine (8a). a CPj analog of chloracizine, showed antidepressive efficacy equivalent to imipramine. 

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