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Psychotropic Use during Pregnancy
Published in “Bert” Bertis Britt Little, Drugs and Pregnancy, 2022
An active metabolite of imipramine, desipramine, is used to treat depression. It has sedative and anticholinergic effects, but they are much less severe than are those of imipramine. One in 31 infants whose mothers were treated with desipramine during the first trimester was malformed (Briggs et al., 2021), a rate which is not increased. Similar to imipramine, neonatal symptoms consistent with withdrawal were observed when the drug was used taken throughout gestation (Webster, 1973).
Pharmacotherapies for PTSD and Substance Use Disorders
Published in Anka A. Vujanovic, Sudie E. Back, Posttraumatic Stress and Substance Use Disorders, 2019
Lorig K. Kachadourian, Kevin P. Jensen, Mehmet Sofuoglu, Ismene Petrakis
In a more recent study, Petrakis et al. (2012) investigated the efficacy of paroxetine, an SSRI, relative to desipramine, a norepinephrine reuptake inhibitor, among 88 military veterans (predominantly male) with PTSD and AUD. They also evaluated the efficacy of naltrexone as a treatment adjunct, relative to a placebo adjunct (Petrakis et al., 2012). Subjects were randomly assigned to the following four treatment groups under double-blind conditions: (1) paroxetine and naltrexone, (2) paroxetine and placebo, (3) desipramine and naltrexone, and (4) desipramine and placebo. Alcohol consumption decreased significantly over time for all four groups with results favoring desipramine over paroxetine for most alcohol consumption outcomes (e.g., percentage of heavy drinking days, drinks per drinking day). Naltrexone did not outperform placebo with regard to consumption outcomes, although there was a significant difference in craving such that those assigned to naltrexone reported significantly greater decreases in alcohol craving than those assigned to placebo. None of the medications were associated with significant between-group differences on PTSD outcomes (i.e., CAPS total scores).
Anxiolytics: Predicting Response/Maximizing Efficacy
Published in Mark S. Gold, R. Bruce Lydiard, John S. Carman, Advances in Psychopharmacology: Predicting and Improving Treatment Response, 2018
Panic attacks stop after about 3 weeks of adequate doses of a tricyclic or a monoamine oxidase inhibitor. Tricyclics are safer than MAOIs and do not require a careful diet. Specifically, desipramine is very effective and among tricyclics has a minimum of anticholinergic and antihistamine side effects. Any of these drugs, including desipramine, is associated with peripheral hypersympathetic side effects for the first few weeks of treatment before tolerance develops to them. This early period can be associated with increased panic attacks, and patients usually perceive themselves to be worse in these weeks. Often they flee medication for these reasons. Also, they feel that they are being controlled by a drug that they sense by these side effects. In their compulsive personality structure, they stubbornly insist to control themselves. This is another major source of medication noncompliance. Patients who refuse medication don’t get better. Compliance with treatment can be assured by (1) warning the patient in advance about side effects and how she is likely to feel about them, (2) emphasizing that they are temporary, (3) not increasing desipramine precipitously, (4) using two drugs in combination, and (5) measurement of drug levels to assure the patient is taking the drug (s) and the level is appropriate.
Neuroprotective benefits of grape seed and skin extract in a mouse model of Parkinson’s disease
Published in Nutritional Neuroscience, 2021
Sarah Ben Youssef, Guillaume Brisson, Hélène Doucet-Beaupré, Anne-Marie Castonguay, Charles Gora, Mohamed Amri, Martin Lévesque
The intrastriatal stereotaxic unilateral injection of 6-OHDA was used to establish a model of PD (Stott et al., 2014). The mice received a special diet consisting of peanut butter, mashed pellets and DietGel® Boost (ClearH2O, Westbrook, ME) 3 days prior to surgery to help them cope with postsurgical weight loss. Desipramine (2.5 mg/mL; Sigma) was administered ip at a dose of 10 mL/kg body weight 15 min prior to the animal being anesthetized to increase the selectivity and efficacy of the 6-OHDA-induced lesions (Thiele et al., 2012). The animals were anesthetized with 4% isoflurane and immobilized in a stereotaxic apparatus (Stoelting, Wood Dale, IL). Lesions were made by the unilateral injection of 6-OHDA (4.5 μg total dose, 1.5 μL/site) into the right striatum at the following coordinates: AP: +0.8 mm; ML: +1.6 mm; DV: −2.4 mm (DV, taken from the surface of the brain) from bregma (Bradley et al., 2007). The sham-operated animals received an injection of vehicle only (0.2% ascorbate in 0.9% sodium chloride) at the same coordinates. The 6-OHDA solution was prepared fresh, protected from light to avoid auto-oxidation and administered at a rate of 0.5 μL/min using a 5 μL microinjector. The syringe was left in place for 5 min after 6-OHDA delivery before slowly retracting it to allow for toxin diffusion and prevent toxin reflux. The mice were then sutured and provided with postsurgical care with daily subcutaneous injections of saline (0.9% NaCl) and free access to the special diet described above to avoid drastic postsurgery weight loss.
Antidepressants with different mechanisms of action show different chronopharmacological profiles in the tail suspension test in mice
Published in Chronobiology International, 2019
Hiroshi Kawai, Reiko Iwadate, Takuya Ishibashi, Naomi Kudo, Yoichi Kawashima, Atsushi Mitsumoto
To analyze the possibility that the difference in tissue drug levels among different ZTs causes the chronopharmacological activity observed in TST, we analyzed the plasma and brain drug levels after administration using the same treatment schedule for TST. As the dosing time-dependent difference in antidepressant activity was large between ZT1 and ZT13 in all four tested drugs (Figure 2), tissue drug levels were analyzed at these ZTs. Desipramine, an imipramine metabolite, has antidepressant activity and has comparable potency as that of imipramine itself (Tatsumi et al. 1997). Therefore, desipramine levels were also measured in imipramine-treated mice. The results are shown in Figures 6 and 7. The differences between ZT1 and ZT13 were small and not significant in all four drugs.
Sitagliptin rescues memory deficits in Parkinsonian rats via upregulating BDNF to prevent neuron and dendritic spine loss
Published in Neurological Research, 2018
Jing Li, Shuhu Zhang, Chenye Li, Mei Li, Lan Ma
Rats were anesthetized by 10% chloral hydrate via i.p. injection and restrained in a stereotaxic apparatus (8001, RWD Life Science). The injection target is right substantia nigra as the following the coordinates below: anteroposterior from bregma (AP) = −2.2 mm, mediolateral from the midline (ML) = 4.5 mm and dorsoventral from the skull (DV) = −6.7 mm. Following the literature method [17], desipramine (25 mg/kg, i.p.) was injected 30 min before intra-nigral injection of 6-OHDA to avoid degeneration of noradrenergic neurons. Then, 6-OHDA (8 μg/rat) was infused by infusion pump at the flow rate of 0.2 μl/min into the right substantia nigra. After the injection, the needle was maintained in the brain for an additional 2 min before it was slowly retracted. Similarly, rats in sham group were submitted to the same procedure except giving 6-OHDA. Finally, the wound place of rats was disinfected and sutured.