Unveiling the Promise: A Comprehensive Review of Salpingectomy as a Vanguard for Ovarian Cancer Prevention.

This comprehensive review explores the potential of salpingectomy as a groundbreaking strategy for the prevention of ovarian cancer. The discussion encompasses the biological rationale behind salpingectomy, emphasizing its foundation in the tubal hypothesis, which posits the fallopian tubes as a possible origin site for certain ovarian cancers. Ongoing clinical trials and observational studies provide evolving evidence supporting the safety and efficacy of salpingectomy, particularly in high-risk populations. The procedure's ethical considerations, including its impact on fertility and equitable access, are thoroughly examined. Implications for clinical practice underscore the importance of informed decision-making, risk-benefit assessments, and the integration of emerging evidence into reproductive health discussions. Looking ahead, the future landscape of ovarian cancer prevention involves continued research, technological innovations, and collaborative efforts to ensure a holistic and evidence-based approach. The goal is to forge a future where ovarian cancer is not only treatable but also preventable, with salpingectomy potentially playing a pivotal role in this transformative journey.

Cutaneous Manifestations and Neurological Diseases.

Our skin and nervous system are tightly connected. Numerous dermatomes on our skin provide sensory information to the brain. Because skin changes can occasionally be the first sign of a neurological problem, understanding skin alterations is crucial as it can indicate early about the underlying condition, which can affect the prognosis of the disease. In these cases, the dermatologists' and neurologists' skills are complementary to each other. In this article, we have categorized diseases with neuro-cutaneous manifestations under different headings, such as infections, metabolic diseases, connective tissue disorders, genodermatoses, nutritional deficiency, and the diagnostic criteria of some commonly encountered diseases. Through tabulation, it has been observed that this categorization can serve as a useful reference for managing day-to-day patients who are either diagnosed with the diseases mentioned above or suspected to have the conditions.

An Unusual Presentation of Glioependymal Cyst Encroaching Neuronal Parenchyma in an Elderly Female: A Case Report.

A glioependymal cyst (GEC) is a rare type of cyst that occurs within the brain and spinal cord. A 42-year-old male patient with a cystic lesion in the right frontal lobe was admitted to the hospital to have his headache, vertigo, and body spasms evaluated. MRI scans showed a mass in the right side of the frontal lobe which caused a mass effect over the lateral ventricle and corpus callosum. The patient became symptom-free after the craniotomy, followed by fenestration of cortices and cyst wall removal.

Infected Dentigerous Cyst and its Conservative Management: A Report of Two Cases.

AIM: To check the efficacy of decompression technique in children with dentigerous cysts. BACKGROUND: Most commonly occurring odontogenic cysts in the oral cavity are radicular cysts and dentigerous cysts.1 According to Kramer, a cyst is defined as a pathological cavity having fluid, semi-fluid, or gaseous contents, which is not created by the accumulation of pus. A cyst which is lined by epithelium is known as a true cyst and that which is not lined by epithelium known as a pseudocyst.2 The dictionary meaning of dentigerous is "structures resembling teeth".3 A dentigerous cyst is found enveloping the crown of an unerupted, embedded, or submerged tooth by the expansion of its follicle till the neck of the tooth.1 It is not unusual for a dentigerous cyst to mimic a radicular cyst, especially when the cyst is associated with a pulpectomized or carious primary tooth and its unerupted permanent successor. This article presents two cases of infected dentigerous cysts. The first case was of a female patient associated with tooth 45; and another case was of a male patient associated with tooth 35. The infected dentigerous cyst in both the cases was treated with the most conservative option available, i.e., decompression technique. CASE DESCRIPTION: In this article, two cases of infected dentigerous cysts are discussed, in which one case deals with the female patient associated with tooth 45 and the other case deals with the male patient associated with tooth 35. The infected dentigerous cysts in both the cases were treated conservatively, i.e., with the decompression technique. CONCLUSION: The present case report states that the decompression technique may be the most conservative method available for managing dentigerous cysts in children. HOW TO CITE THIS ARTICLE: Patil AS, Jathar PN, et al. Infected Dentigerous Cyst and its Conservative Management: A Report of Two Cases. Int J Clin Pediatr Dent 2019;12(1):68-72.

Comparison of Microleakage and Penetration Depth between Hydrophilic and Hydrophobic Sealants in Primary Second Molar.

INTRODUCTION: Optimal pit and fissure sealing is determined by surface preparation techniques and choice of materials. The performance of pit and fissure sealant materials has been intensively investigated, yet no single product is reported as an ideal sealant. In children, moisture control during cavity preparation is always a big challenge, and hence, hydrophilic sealants have been developed. AIM: To compare the microleakage and penetration depth of hydrophilic and hydrophobic sealants using acid-etching on dry and moist surfaces. MATERIALS AND METHODS: Recently, extracted 28 2nd primary molars are assigned to two groups (hydrophobic group I; hydrophilic group II) depending on the surface condition (dry group: A1 and B1; moist group: A2 and B2) of 7 teeth in each group. Samples from group A1 and B1 are cleaned and dried with a 3-way syringe and etched with etching gel, and sealant is applied to the fissures and cured with visible light. Sample from A2 and B2 are immersed in 0.1 mL of fresh whole human saliva for 20 seconds and dried using a pellet cotton, and the same procedure is carried out. All samples are subjected to 1000 thermal cycles and sectioned to compare the depth of penetration and microleakage. Sections will be examined under light microscope and analyzed using an image analysis software (SigmaScan). RESULTS: The least microleakage was seen with hydrophilic sealant under moist surface condition, and the depth of penetration of hydrophobic sealant was found to be better than that of hydrophilic sealant in both dry and moist surface conditions. CONCLUSION: Hydrophilic pit and fissure sealants showed higher tolerance to saliva contamination with less microleakage, but in terms of penetration ability hydrophobic sealants were found to be superior. HOW TO CITE THIS ARTICLE: Gawali PN, Chaugule VB, Panse AM. Comparison of Microleakage and Penetration Depth between Hydrophilic and Hydrophobic Sealants in Primary Second Molar. Int J Clin Pediatr Dent 2016;9(4):291-295.

Lesch-Nyhan Syndrome: Disorder of Self-mutilating Behavior.

Lesch-Nyhan syndrome (LNS), a rare inborn error of metabolism, is characterized by self-injurious behavior, which results in partial or total destruction of oral and perioral tissues and/ or fingers. Persistent self-injurious behavior (biting the fingers, hands, lips, and cheeks; banging the head or limbs) is a hallmark of the disease. Prevention of self-mutilation raises significant difficulties. A case of a 10-month-old boy with aggressive behavior and severe lower lip injuries is presented. How to cite this article: Jathar P, Panse AM, Jathar M, Gawali PN. Lesch-Nyhan Syndrome: Disorder of Self-mutilating Behavior. Int J Clin Pediatr Dent 2016;9(2):139-142.

Identification of three cytochrome P450 isozymes involved in N-demethylation of citalopram enantiomers in human liver microsomes.

Using in vitro techniques, the present study demonstrates that CYP2D6, and 3A4 are involved in N-demethylation of citalopram (CIT) enantiomers. Human liver microsome incubations performed with specific inhibitors of these three CYP isozymes have shown up to 60% inhibition of demethylcitalopram production. cDNA expressed human cytochrome P-450 3A4, 2C19 and 2D6 isozymes, but not CYP1A2, were identified to be involved in N-demethylation of CIT enantiomers. Kinetics using cDNA expressed CYP2C19 and CYP3A4 show K(m) values in the same range: 198 microM, 211 microM for CYP2C19 and 169 microM, 163 microM for CYP3A4 for S- and R-CIT demethylation, respectively. In contrast, kinetics using cDNA expressed CYP 2D6 show a K(m) of 18 microM and 22 microM for S- and R-CIT demethylation, respectively. Nevertheless, kinetics using cDNA expressed CYP2C19 and 3A4 have a range of Vmax values ten times higher than that of CYP2D6. For this reason, intrinsic clearance values (Vmax/K(m)) for S- and R-CIT were within a small range for these three isozymes: 0.25 to 0.39 microliter h-1 x pmol-1 of CYP. CYP2D6 has an opposite stereoselectivity in the biotransformation of CIT enantiomers than CYP2C19 and 3A4; the S/R ratios of the intrinsic clearance were 0.71, 1.57 and 1.37, respectively. Taking into account that CYP isozymes are expressed at various levels, CYP2D6, which is expressed at lower levels than CYP2C19 and CYP3A4, plays a minor role in the biotransformation of CIT enantiomers. These results confirm that the use of cDNA expressed CYP isozymes is a potent tool for the measurement of kinetic constants and help to predict clearance modifications of CIT enantiomers, especially in poor metabolizers of mephenytoin (with a CYP2C19 deficiency) or patients comedicated with potent CYP2C19 or 3A4 inhibitor(s). For instance, fluvoxamine (100 microM) inhibits CIT N-demethylation by 64% in microsomes.

Neuroendocrine effects of a 20-mg citalopram infusion in healthy males. A placebo-controlled evaluation of citalopram as 5-HT function probe.

Pharmacokinetic measurements, neuroendocrine responses, and side effects profiles of intravenous infusions of 20 mg citalopram over 30 minutes during the early afternoon have been studied. Eight healthy male volunteers were enrolled in a placebo- (saline) controlled, single-blind, cross-over protocol. Plasma concentrations of the parent compound showed a double exponential decay. Demethyl and didemethyl metabolites were not detectable, but low concentrations of the propionic acid derivative of citalopram were found. Determination of the citalopram enantiomers yielded a balanced S(+)/R(-) ratio of 0.9 to 1.2. The endocrine response to the drug was characterized by significant increases in plasma prolactin and cortisol. Except for one subject, who developed pronounced side effects, human growth hormone showed a surge following saline that was inhibited following citalopram. Rectal temperature and heart rate were not affected and tolerability was favorable. Because of citalopram's extremely high selectivity for the presynaptic 5-hydroxytryptamine nerve terminals, the present data suggest that it might be a promising tool for the investigation of serotonergic function in the human brain in vivo.

In vitro metabolism of citalopram by monoamine oxidase B in human blood.

The metabolism of the antidepressant citalopram (CIT) by monoamine oxidase B (MAO-B) was studied in vitro. In incubations with blood of nine healthy volunteers R-(P=0.015) and S-(P=0.0034) CIT propionic acid (CITPROP) production was correlated with the number of platelets. S-CITPROP production was 5.6 times higher than R-CITPROP production and in incubations containing the MAO-B inhibitor deprenyl, racemic CITPROP production was diminished to 9.1%. To our knowledge, this is the first time that MAO-B activity in blood is shown with an antidepressant as substrate. As MAO is strongly expressed in human brain, this observation suggests that this enzymatic system may be implicated in drug metabolism in the CNS.

Simultaneous determination of human plasma levels of citalopram, paroxetine, sertraline, and their metabolites by gas chromatography-mass spectrometry.

A gas chromatography-mass spectrometry method is presented which allows the simultaneous determination of the plasma concentrations of the selective serotonin reuptake inhibitors citalopram, paroxetine, sertraline, and their pharmacologically active N-demethylated metabolites (desmethylcitalopram, didesmethylcitalopram, and desmethylsertraline) after derivatization with the reagent N-methyl-bis(trifluoroacetamide). No interferences from endogenous compounds are observed following the extraction of plasma samples from six different human subjects. The standard curves are linear over a working range of 10-500 ng/mL for citalopram, 10-300 ng/mL for desmethylcitalopram, 5-60 ng/mL for didesmethylcitalopram, 20-400 ng/mL for sertraline and desmethylsertraline, and 10-200 ng/mL for paroxetine. Recoveries measured at three concentrations range from 81 to 118% for the tertiary amines (citalopram and the internal standard methylmaprotiline), 73 to 95% for the secondary amines (desmethylcitalopram, paroxetine and sertraline), and 39 to 66% for the primary amines (didesmethylcitalopram and desmethylsertraline). Intra- and interday coefficients of variation determined at three concentrations range from 3 to 11% for citalopram and its metabolites, 4 to 15% for paroxetine, and 5 to 13% for sertraline and desmethylsertraline. The limits of quantitation of the method are 2 ng/mL for citalopram and paroxetine, 1 ng/mL for sertraline, and 0.5 ng/mL for desmethylcitalopram, didesmethylcitalopram, and desmethylsertraline. No interferences are noted from 20 other psychotropic drugs. This sensitive and specific method can be used for single-dose pharmacokinetics. It is also useful for therapeutic drug monitoring of these three drugs and could possibly be adapted for the quantitation of the two other selective serotonin reuptake inhibitors on the market, namely fluoxetine and fluvoxamine.

Use of plasma level monitoring of antidepressants in clinical practice. Towards an analysis of clinical utility.

The use of therapeutic drug monitoring (TDM) in the authors' hospital was studied for various antidepressants (maprotoline, clomipramine, imipramine, desipramine, nortriptyline, amitriptyline) in a two part-study (retrospective and prospective). Criteria for appropriate requests for TDM from the resident psychiatrists and for appropriate interpretation of the results were defined according to a clinical effectiveness/toxicity model. For this purpose, a "therapeutic window" (between 150 and 250 ng/ml) was chosen. Whereas the quality of the TDM requests varied in the two studies (41% and 26% inappropriate requests in the retrospective and prospective study respectively), the interpretation of the results was the same in the two studies (19% inappropriate therapeutic adjustments). Considering both the inappropriate requests and the inappropriate therapeutic adjustments, if appears that 52% of the assays in the retrospective study and 40% in the prospective study are inappropriate. In common with previous studies with other drugs, the present study concludes that the use of the antidepressant TDM could be improved. To this end, closer attention must be given to the nature of TDM requests.

Analysis of enantiomers of citalopram and its demethylated metabolites in plasma of depressive patients using chiral reverse-phase liquid chromatography.

A stereospecific high-performance liquid chromatography (HPLC) method has been developed for the analysis of the underived enantiomers of citalopram (CIT) and its N-demethylated metabolites in plasma. Using fluorescence detection, the limit of quantification for each enantiomer is 3 ng/ml. CIT N-oxide and the CIT propionic acid derivative are not extracted by the procedure used. Inter- and intraday validations of the method using reverse-phase mode HPLC on separate acetylated beta-cyclobond columns showed the sensitivity of this assay to be suitable for pharmacokinetic studies of the enantiomers of these compounds. Plasma levels of the enantiomers and the demethylated metabolites of CIT have been determined during routine therapeutic drug monitoring (TDM) in 29 depressive patients treated with varying dosages (20-80 mg/day) of CIT. Concentrations of S-(+)-CIT, which is considered the most potent selective serotonin reuptake inhibitors (SSRI) of the CIT and desmethylcitalopram (DCIT) enantiomers, varied between 24-49% (mean +/- sd, 35% +/- 5%) of the concentrations of total CIT. There were highly significant correlations between S-(+)-CIT and R-(-)-CIT levels (r = 0.866; p < 0.0001) and between S-(+)-DCIT and R-(-)-CIT (r = 0.932; p < 0.0001). The co-medications seemed to have little influence on enantiomer ratios. These results suggest the need for studies on the relationships between clinical response and plasma levels of CIT enantiomers.

Analysis of the enantiomers of citalopram and its demethylated metabolites using chiral liquid chromatography.

A procedure using a chirobiotic V column is presented which allows separation of the enantiomers of citalopram and its two N-demethylated metabolites, and of the internal standard, alprenolol, in human plasma. Citalopram, demethylcitalopram and didemethylcitalopram, as well as the internal standard, were recovered from plasma by liquid-liquid extraction. The limits of quantification were found to be 5 ng/ml for each enantiomer of citalopram and demethylcitalopram, and 7.5 ng/ml for each enantiomer of didemethylcitalopram. Inter- and intra-day coefficients of variation varied from 2.4% to 8.6% for S- and R-citalopram, from 2.9% to 7.4% for S- and R-demethylcitalopram, and from 5.6% to 12.4% for S- and R- didemethylcitalopram. No interference was observed from endogenous compounds following the extraction of plasma samples from 10 different patients treated with citalopram. This method allows accurate quantification for each enantiomer and is, therefore, well suited for pharmacokinetic and drug interaction investigations. The presented method replaces a previously described highly sensitive and selective high-performance liquid chromatography procedure using an acetylated 3-cyclobond column which, because of manufactural problems, is no longer usable for the separation of the enantiomers of citalopram and its demethylated metabolites.

Marked increase of venlafaxine enantiomer concentrations as a consequence of metabolic interactions: a case report.

On three occasions, unusually high trough plasma concentrations of venlafaxine were measured in a patient phenotyped and genotyped as being an extensive CYP2D6 metabolizer and receiving 450 mg/day of venlafaxine and multiple comedications. Values of 1.54 and of 0.60 mg/l of venlafaxine and O-desmethylvenlafaxine, respectively, were determined in the first blood sample, giving an unusually high venlafaxine to O-desmethylvenlafaxine ratio. This suggests an impaired metabolism of venlafaxine to O-desmethylvenlafaxine, and is most likely due to metabolic interactions with mianserin (240 mg/day) and propranolol (40 mg/day). Concentration of (S)-venlafaxine measured in this blood sample was almost twice as high as (R)-venlafaxine ((S)/(R) ratio: 1.94). At the second blood sampling, after addition of thioridazine (260 mg/day), which is a strong CYP2D6 inhibitor, concentrations of venlafaxine were further increased (2.76 mg/l), and concentrations of O-desmethylvenlafaxine decreased (0.22 mg/l). A decrease of the (S)/(R)-venlafaxine ratio (-20%) suggests a possible stereoselectivity towards the (R)-enantiomer of the enzyme(s) involved in venlafaxine O-demethylation at these high venlafaxine concentrations. At the third blood sampling, after interruption of thioridazine, concentrations of venlafaxine and O-desmethylvenlafaxine were similar to those measured in the first blood sample. This case report shows the importance of performing studies on the effects of either genetically determined or acquired deficiency of metabolism on the kinetics of venlafaxine.

Determination of the enantiomers of citalopram, its demethylated and propionic acid metabolites in human plasma by chiral HPLC.

A stereoselective HPLC assay has been developed to analyze the enantiomers of citalopram and of its three main metabolites in plasma after their separation on a Chiracel OD column. Using a fluorescence detector, the limit of quantification in plasma samples was 15, 4, 5 and 2 ng/ml for the enantiomers of citalopram (CIT), desmethylcitalopram (DCIT), didesmethylcitalopram (DDCIT), and for the citalopram propionic acid derivative (CIT-PROP), respectively. Except for CIT, all metabolites were derivatized with achiral reagents. Identification of the enantiomers was realized with an optical rotation detector which showed that the enantiomers invert their rotation depending on the polarity and nature of the solvent. Under varying conditions, a racemization study has shown that the pure enantiomers of CIT and its demethylated metabolites are configurationally stable. Preliminary results obtained with five patients treated with CIT show a mean S/R ratio of 0.7 for both CIT and its active metabolite DCIT and of 3.6 for CIT-PROP in plasma. This suggests that the pharmacologically relevant (+)-(S)-isomers of CIT and DCIT could be preferentially and stereoselectively metabolized to CIT-PROP.

Tricyclic antidepressant plasma levels after augmentation with citalopram: a case study.

In a depressed patient, the addition of citalopram 40-60 mg per day to treatment with amitriptyline 75 mg per day had no effect on the plasma levels of amitriptyline and nortriptyline, but it led to clinical improvement without the appearance of adverse effects. This and similar findings in four other patients comedicated with citalopram and amitriptyline (2 patients), clomipramine or maprotiline suggest that citalopram differs from other selective serotonin reuptake inhibitors, such as fluvoxamine and fluoxetine, which have been shown to increase tricyclic antidepressant plasma levels.

Determination of plasma levels of citalopram and its demethylated and deaminated metabolites by gas chromatography and gas chromatography-mass spectrometry.

Sensitive and specific methods based on gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS) for the determination of levels of citalopram, desmethylcitalopram and didesmethylcitalopram in the plasma of patients treated with citalopram are presented, as well as a GC-MS procedure for the assay of the citalopram propionic acid derivative. After addition of a separate internal standard for each drug, liquid-solvent extraction is used to separate the basic compounds from the acid compounds. The demethylated amines are derivatized with trifluoroacetic anhydride, and the acid metabolite with methyl iodide. GC-MS is performed in the electron impact mode, as mass spectrometry by the (positive-ion) chemical ionization mode (methane and ammonia) appeared to be unsuitable. The limits of quantification were 1 ng/ml for citalopram and desmethylcitalopram and 2 ng/ml for the other metabolites. The correlation coefficients for the calibration curves (range 10-500 ng/ml) were > or = 0.999 for all compounds, whether determined by GC or GC-MS.

In vitro biotransformation of the selective serotonin reuptake inhibitor citalopram, its enantiomers and demethylated metabolites by monoamine oxidase in rat and human brain preparations.

This study was conducted to identify enzyme systems eventually catalysing a local cerebral metabolism of citalopram, a widely used antidepressant of the selective serotonin reuptake inhibitor type. The metabolism of citalopram, of its enantiomers and demethylated metabolites was investigated in rat brain microsomes and in rat and human brain mitochondria. No cytochrome P-450 mediated transformation was observed in rat brain. By analysing H2O2 formation, monoamine oxidase A activity in rat brain mitochondria could be measured. In rat whole brain and in human frontal cortex, putamen, cerebellum and white matter of five brains monoamine oxidase activity was determined by the stereoselective measurement of the production of citalopram propionate. All substrates were metabolised by both forms of MAO, except in rat brain, where monoamine oxidase B activity could not be detected. Apparent Km and Vmax of S-citalopram biotransformation in human frontal cortex by monoamine oxidase B were found to be 266 microM and 6.0 pmol min(-1) mg(-1) protein and by monoamine oxidase A 856 microM and 6.4 pmol min(-1) mg(-1) protein, respectively. These Km values are in the same range as those for serotonin and dopamine metabolism by monoamine oxidases. Thus, the biotransformation of citalopram in the rat and human brain occurs mainly through monoamine oxidases and not, as in the liver, through cytochrome P-450.

Dextromethorphan and mephenytoin phenotyping of patients treated with thioridazine or amitriptyline.

The metabolism of most tricyclic antidepressants and some phenothiazine neuroleptics is under the genetic control of hepatic cytochrome P-450IID6, which also regulates the metabolism of dextromethorphan. This study investigated the effect of treatment with amitriptyline or thioridazine on testing for genetically regulated efficiency of the metabolism of dextromethorphan and mephenytoin. One group of 33 patients was treated with 150 mg amitriptyline a day (the AMI group); 25 other patients received a daily dose of thioridazine, either 200 mg (200-THD group; n = 7) or 400 mg (400-THD group; n = 18). Before and after 10 days of this treatment, all patients were tested with 25 mg dextromethorphan and 100 mg mephenytoin to determine their pharmacogenetic status with respect to their hepatic drug oxidizing systems (cytochrome P-450IID6 and P-450 MP). Two patients were poor metabolizers (PMs) of dextromethorphan and three of mephenytoin. Treatment with either psychotropic drug was without significant effect on the metabolism of mephenytoin, but both amitriptyline and thioridazine increased significantly the metabolic ratio of dextromethorphan/dextrorphan. Thioridazine had the effect of changing the pharmacogenetic status of 15 efficient metabolizers of dextromethorphan to poor metabolizers; amitriptyline did not have such an effect. There was no significant correlation between day-11 plasma levels of thioridazine, mesoridazine, or sulforidazine and the metabolism of dextromethorphan, but there was a correlation between the metabolism of dextromethorphan and plasma levels of amitriptyline and nortriptyline. Amitriptyline (p less than 0.05), but not thioridazine, decreases the ratio of conjugated/total dextrorphan in urine.(ABSTRACT TRUNCATED AT 250 WORDS)

Monitoring tricyclic antidepressant concentrations in serum by fluorescence polarization immunoassay compared with gas chromatography and HPLC.

The fluorescence polarization immunoassay (FPIA) developed by Abbott to diagnose intoxication with tricyclic antidepressants was adapted for therapeutic drug monitoring and validated with chromatograpic methods to investigate its potential for this use. We compared serum concentrations of tricyclic antidepressants in vivo and in vitro obtained by FPIA with those by gas chromatography and HPLC. For amitriptyline, imipramine, clomipramine, and doxepin, the detection limit of the FPIA was 72, 71, 64, and 72 nmol/L (approximately 20 micrograms/L), respectively; that by gas chromatography was 18, 18, and 16 nmol/L (approximately 5 micrograms/L) for amitriptyline, imipramine and clomipramine, respectively; with HPLC the lower limit of detection for doxepin was 36 nmol/L (10 micrograms/L). The intra- and interassay CVs ranged from 3% to 6%. In patients being treated with amitriptyline, imipramine, clomipramine, and doxepin, at steady-state the correlation coefficients between FPIA and GC/HPLC results for split samples were 0.95, 0.92, 0.90 and 0.70, respectively. However, the slopes were close to unity only for amitriptyline and doxepin, being 0.6 for imipramine and 1.9 for clomipramine.