Tricyclic antidepressants Imipramine

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). 

Metabolism converts a lipophilic molecule into a more hydrophilic (water-loving) metabolite that can be excreted in urine by the kidneys. In the majority of cases the drug is detoxified, or made pharmacologically inactive by this metabolic breakdown. However, a few drugs need to be metabolised to become psychoactive for instance, the sedative-hypnotic chloral hydrate is converted to the active metabolite trichloroethanol. In this case the parent molecule is referred to as a prodrug. With many drugs, both the parent compound and its metabolites are psychoactive. An example of this is the tricyclic antidepressant imipramine which is metabolised to desipramine, with... 

Many neurotransmitters are inactivated by a combination of enzymic and non-enzymic methods. The monoamines - dopamine, noradrenaline and serotonin (5-HT) - are actively transported back from the synaptic cleft into the cytoplasm of the presynaptic neuron. This process utilises specialised proteins called transporters, or carriers. The monoamine binds to the transporter and is then carried across the plasma membrane it is thus transported back into the cellular cytoplasm. A number of psychotropic drugs selectively or non-selectively inhibit this reuptake process. They compete with the monoamines for the available binding sites on the transporter, so slowing the removal of the neurotransmitter from the synaptic cleft. The overall result is prolonged stimulation of the receptor. The tricyclic antidepressant imipramine inhibits the transport of both noradrenaline and 5-HT. While the selective noradrenaline reuptake inhibitor reboxetine and the selective serotonin reuptake inhibitor fluoxetine block the noradrenaline transporter (NAT) and serotonin transporter (SERT), respectively. Cocaine non-selectively blocks both the NAT and dopamine transporter (DAT) whereas the smoking cessation facilitator and antidepressant bupropion is a more selective DAT inhibitor. 

There are four classes of antidepressants tricyclic antidepressants (imipramine, trimipramine, amitriptyline, doxepin, desipramine, protriptyline, nortriptyline, amoxapine, maprotiline) monoaminooxidase (MAO) inhibitors (phenelzine, isocarboxazid, tranylcypromine) second-generation antidepressants or atypical antidepressants, which are a chemically dissimilar group of recently proposed drugs (bupropion, trazodone, fluoxetine) and amphetamines and other stimulators of the CNS (dextroamphetamine, methylphenidate). 

In the case of social anxiety disorder, research suggests that some of the antidepressants that are effective in other anxiety disorders do not work to ease the symptoms of social anxiety disorder. This is true of the tricyclic antidepressant imipramine and fluoxetine (Prozac). The first line of treatment for the generalized form of social anxiety disorder is an SSRI such as paroxetine or sertraline. 

The discovery that drugs elevating extracellular levels of noradrenaline and/or serotonin have analgesic potential was circumstantial. In I960, Paoli et al. reported that during an attempt to treat reactive depression in chronic pain patients with the tricyclic antidepressant imipramine they observed an improvement of the patients neuralgic pain. Subsequently, it became well established that antidepressant drugs can improve both depression and chronic pain states. 

Tricyclic antidepressants. Imipramine and clomipramine have been the most extensively studied of the tricyclic antidepressants and both have demonstrated efficacy in treating panic disorder. Other tricyclic antidepressants that have shown some evidence of efficacy include desipramine, doxepin, amitriptyline, and nortriptyline. 

Reuptake Norepinephrine transporter Tricyclic antidepressants (imipramine, f) Tricyclic norepinephrine reuptake inhibitors (desipiamine, ) Selective norepinephrine reuptake inhibitors (reboxetine, ) Dual serotonin/ norepinephrine reuptake inhibitors (venlafaxine, J.)... 

In addition to known antidepressants increasing endogenous opioids, opioid ligands have also been administered to depressed patients to determine if opioid compounds have clinical efficacy to treat depression. The opioid ligand cyclazocine improved symptoms in severely depressed, chronically ill mental patients in an open clinical trial and in clinical trials with patients unresponsive to the tricyclic antidepressant imipramine [16]. Intravenous (5-endorphin infusions improved mood in depressed patients in open case studies [17] and in depressed patients in a double-blind placebo-controlled study [18,19]. However, one study found a trend to improve depression scores in patients after acute and chronic (5-endorphin infusions, but it was not significant [20]. 

Fig. 1.5 The tricyclic antidepressants (imipramine and maprotiline) are characterized by a dihedral angle of 55° to 55° between the two benzo rings this angle is only 25° for the tricyclic neuroleptics (chlorpromazine, chlorprothixene) [12].

Brorson L, Wennerblom B. Electrophysiological methods in assessing cardiac effects of the tricyclic antidepressant imipramine. Acta Med Scand 1978 203(5) 429-32. 

Tricyclic antidepressants. Imipramine, amitriptyline and nortriptyline are effective, especially for nocturnal but also for daytime incontinence. Their parasympathetic blocking (antimuscarinic) action is probably in part responsible but imipramine... 

Dryness of the mouth may also result in other problems. For example, the tricyclic antidepressant imipramine (e.g., Tofranil) can cause persistent dryness of the mouth. If nitroglycerin tablets are administered sublingually for the management of exertional angina, the relief of the symptoms may be delayed due to the slower dissolution of the sublingual tablets. 

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. 

Adrenergic agents and/or tricyclic antidepressants may be used to induce ejaculation ex copula (also known as "chemical ejaculation") in stallions that have inadequate erection prior to or following insertion. Ejaculation is either observed within 3 min of (associated with the onset of sedation) or 15-20 min after (associated with recovery from sedation) the i.v. administration of the U2 adrenoceptor agonist xylazine (0.66mg/kg) (McDonnell 1999). Ejaculation typically occurs 10-60min after the i.v. administration of the tricyclic antidepressant imipramine (2.2mg/kg) (McDonnell 1999). These two medications may be used in combination imipramine is administered p.o. at a dose rate of 0.075-2.0 mg/kg followed 1-2 h later by xylazine (0.3 mg/kg i.v.). Ejaculation occurs 3-15 min after the xylazine (McDonnell 1993, McDonnell 2001). PGF2a i.m. at 0.005-0.01 mg/kg results in ejaculation 5-90 min later (McDonnell 1999). 

Tricyclic antidepressants Imipramine Selective serotonin-reuptake Fluoxetine... 

Carbamazepine is structurally related to phenytoin and to the tricyclic antidepressant, imipramine. The oral bioavailability of carbamazepine, which may depend on a particular pharmaceutical preparation, is 75 to 85%. After absorption, it is bound to plasma proteins to the extent of 60 to 70%. Carbamazepine is metabolized to its 10,11-epoxide and 10,11-dihydroxide derivatives, some of which are... 

The prototypes for this class are quinidine, disopyramide, and procainamide. This class also includes amiodarone and the tricyclic antidepressant imipramine, which has antiarrhythmic properties. 

The client with major depressive disorder is suicidal. The client was prescribed the tricyclic antidepressant imipramine (Tofranil) 3 weeks ago. Which priority intervention should the nurse implement ... 

B. In addition, presumably because its chemical structure is similar to that of the tricyclic antidepressant imipramine, acute carbamazepine overdose can cause seizures and cardiac conduction disturbances. 

Four patients taking tricyclic antidepressants (imipramine, clomipramine, dibenzepin) and one taking viloxazine relapsed into depression when they took co-trimoxazole (trimethoprim with sulfamethoxazole) for 2 to 9 days. The reasons are not known. Another patient treated for 5 years with alprazolam and imipramine for panic disorder and who had not had panic attacks for several months developed insomnia, anxiety and panic attacks within 6 days of starting to take co-trimoxazole. The panic... 

A potentially related interaction has been reported between tricyclic antidepressants and methylphenidate which acts as an indirectly acting sympathomimetic amine. Cases have been reported (40 ) of patients taking tricyclic antidepressants (imipramine 200 mg, protriptyline 30 mg, and imi-... 

---