- Toxicological findings in suicides - frequency of antidepressant and antipsychotic substances. [Journal Article]
- FSForensic Sci Med Pathol 2018 Nov 05
- The role of psychoactive substances in the treatment of mental disorders and the risk of suicide are major public health issues. This cross-sectional study examined the prevalence of antidepressants ...
The role of psychoactive substances in the treatment of mental disorders and the risk of suicide are major public health issues. This cross-sectional study examined the prevalence of antidepressants and antipsychotics detected in toxicological screenings in suicides. Cases from the Institute of Legal Medicine of the Charité-University Medicine Berlin were reviewed over a 4-year-period. All cases (n = 477) with positive toxicology for antidepressants and antipsychotics in blood or organ tissue were included. Frequencies of the detected substances in non-suicide cases (n = 212; male n = 177, 55.2%; female n = 95, 52.5%) and suicide cases (n = 235; male n = 149, 63.4%; female n = 86, 36.6%) were examined. Tricyclic antidepressants (48.1%) were found most frequently in suicides, followed by atypical neuroleptics (37.0%), selective serotonin reuptake inhibitors (28.1%), typical neuroleptics (17.4%), tetracyclic antidepressants (16.2%) and other substances (8.9%). Alcohol was detected in 37.2% of suicides. The leading cause of death was drug poisoning (35.6%) followed by polytrauma (26.8%) and death by hanging (18.5%). A mental disorder (depression, schizophrenia, bipolar disorder, suicidality) was known in 22.9% of suicides. The most common location of death was the person's own house (63.8%) followed by public places (28.1%) and hospitals (8.1%) The five most common substances in the suicide group were doxepin (20%) citalopram (15.3%), mirtazapine (14.9%), quetiapine (13.6%) and amitriptyline (12.3%). Toxicological findings from cross-sectional studies provide insight into how often certain types of antidepressants and antipsychotics are associated with suicide. A complementary approach is valuable for assessing the risk of suicide during medical treatment because the various available approaches (analysis of suicidal behavior/ideation, toxicity of drugs) each have strengths and limitations.
- Antidepressant Effect of an Orally Administered Dipeptide Mimetic of the Brain-Derived Neurotrophic Factor. [Journal Article]
- ANActa Naturae 2018 Jul-Sep; 10(3):81-84
- Involvement of BDNF in the regulation of neuroplasticity and neurogenesis in the hippocampus, impairment of which underlies the pathophysiology of depression, makes this endogenous protein a promisin...
Involvement of BDNF in the regulation of neuroplasticity and neurogenesis in the hippocampus, impairment of which underlies the pathophysiology of depression, makes this endogenous protein a promising object for the development of new-generation antidepressants with a neurophysiologically based mechanism of action. A low-molecular-weight BDNF mimetic, GSB-106 (a substituted dimeric dipeptide, bis-(N-monosuccinyl- L-seryl-L-lysine) hexamethylenediamide), was designed and synthesized at the Zakusov Institute of Pharmacology. GSB-106 was found to activate BDNF-specific TrkB receptors and their main post-receptor signaling pathways MAPK/ERK and PI3K/AKT. GSB-106 exhibited pronounced antidepressant activity in a rodent test battery at a dose of 0.1 to 1.0 mg/kg administered intraperitoneally. Because oral administration is preferable in the treatment of depression, which is associated with a prolonged duration and outpatient character of pharmacotherapy, we examined the antidepressant properties of GSB-106 administered orally as a pharmaceutical substance (PS) and in tablet dosage form (TDF). In the study, we used the Porsolt forced swim test in rats; a conventional antidepressant, Amitriptyline, was used as a reference drug. The antidepressant activity of GSB-106 was found to retain upon oral administration and to manifest at doses of 0.5-5.0 mg/kg for PS and 0.01-5.0 mg/kg for TDF. The effective dose of TDF was 50-fold lower than that of PS, and the efficacy of tableted GSB-106 exceeded that of Amitriptyline, the "gold standard" in antidepression care. Therefore, GSB-106, both as a substance and as a tablet dosage form, exhibits antidepressant activity when administered orally, which makes it a promising antidepressant agent, the first in the class of BDNF mimetics.
- High-throughput Paper Spray Mass Spectrometry via Induced Voltage. [Journal Article]
- RCRapid Commun Mass Spectrom 2018 Nov 05
- CONCLUSIONS: We have demonstrated the versatility of high-throughput IPS-MS in ambient ionization, which successfully simplified the experimental installation and facilitated the experimental operation. Therefore, we believe that high-throughput IPS-MS analysis will be widely used for discovering drugs and screening reaction, and the present design has a potential for applications in paper chip-MS analysis.
- Irinotecan Alters the Disposition of Morphine Via Inhibition of Organic Cation Transporter 1 (OCT1) and 2 (OCT2). [Journal Article]
- PRPharm Res 2018 Oct 25; 35(12):243
- CONCLUSIONS: Morphine is a substrate of OCT1 and OCT2. Clinician should be aware that the disposition of and thus the response to morphine may be altered by co-administration of an OCT1/2 inhibitor, such as irinotecan.
- Delivery of amitriptyline by intravenous and intraperitoneal administration compared in the same animal by whole-body mass spectrometry imaging of a stable isotope labelled drug substance in mice. [Journal Article]
- EOExpert Opin Drug Deliv 2018 Oct 25; :1-7
- CONCLUSIONS: The method provides a unique way to compare delivery and metabolism of a drug by different administration routes or formulations in the very same animal, eliminating uncertainties caused by animal-to-animal variation and avoiding the use of radioactive labeling.
- Proctalgia and constipation secondary to hypertrophic polyglucosan inclusion body myopathy of the internal anal sphincter: a case report. [Journal Article]
- JMJ Med Case Rep 2018 Oct 24; 12(1):315
- CONCLUSIONS: Hereditary polyglucosan inclusion body myopathy of the internal anal sphincter should be considered in the differential diagnosis of a patient presenting with severe anal pain and constipation in the absence of an anal fissure or sepsis. If medical therapy with calcium antagonists fails to provide symptom relief, lateral internal sphincterotomy should be considered rather than botulinum toxin injection.
- Amitriptyline prevents CPT-11-induced early-onset diarrhea and colonic apoptosis without reducing overall gastrointestinal damage in a rat model of mucositis. [Journal Article]
- SCSupport Care Cancer 2018 Oct 23
- CONCLUSIONS: Prophylactic amitriptyline was able to inhibit early intestinal damage in this rat model of CPT-11-induced GIM, but exacerbated late-onset injury. These findings do not support use of amitriptyline as an approach for mitigation of GIM in this setting.
- Multicentre, double-blind, crossover trial to identify the Optimal Pathway for TreatIng neurOpathic paiN in Diabetes Mellitus (OPTION-DM): study protocol for a randomised controlled trial. [Journal Article]
- TTrials 2018 Oct 22; 19(1):578
- CONCLUSIONS: The study includes direct comparisons of the mainstay treatment for DPNP. This novel study is designed to examine treatment pathways and capture clinically relevant outcomes which will make the results generalisable to current clinical practice. The study will also provide information on health economic outcomes and will include a subgroup study to provide information on whether patient phenotypes predict response to treatment.
- Headache: Tension-Type Headache. [Journal Article]
- FEFP Essent 2018; 473:17-20
- Tension-type headache (TTH) is the most common primary headache disorder, with a worldwide lifetime prevalence of 46% to 78%. TTH causes greater disability and accounts for more missed work days than...
Tension-type headache (TTH) is the most common primary headache disorder, with a worldwide lifetime prevalence of 46% to 78%. TTH causes greater disability and accounts for more missed work days than migraine. The etiology of TTH is thought to be multifactorial, involving genetic and environmental factors. The three subtypes of TTH are infrequent episodic, frequent episodic, and chronic. Patients typically describe headache pain as pressing, dull, and with the sensation of a tight band around the head. Nonprescription analgesics are indicated for management of episodic TTH. Prophylaxis should be considered for patients with chronic TTH, with very frequent episodic TTH, at risk of medication overuse headache, and who are unable to tolerate effective doses of first-line drugs. Amitriptyline is recommended as a first-line drug for prophylaxis. (This is an off-label use of amitriptyline.) Physical and integrative therapies for TTH management include electromyography biofeedback, cognitive behavioral therapy, exercise, massage, and trigger point injection.
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- Anti-allodynic Effect of Mangiferin in Rats With Chronic Post-ischemia Pain: A Model of Complex Regional Pain Syndrome Type I. [Journal Article]
- FPFront Pharmacol 2018; 9:1119
- The present study reproduces chronic post-ischemia pain (CPIP), a model of complex regional pain syndrome type I (CRPS-I), in rats to examine the possible transient and long-term anti-allodynic effec...
The present study reproduces chronic post-ischemia pain (CPIP), a model of complex regional pain syndrome type I (CRPS-I), in rats to examine the possible transient and long-term anti-allodynic effect of mangiferin (MG); as well as its potential beneficial interactions with some standard analgesic drugs and sympathetic-mediated vasoconstriction and vasodilator agents during the earlier stage of the pathology. A single dose of MG (50 and 100 mg/kg, p.o.) decreased mechanical allodynia 72 h post-ischemia-reperfusion (I/R). MG 100 mg/kg, i.p. (pre- vs. post-drug) increased von Frey thresholds in a yohimbine and naloxone-sensitive manner. Sub-effective doses of morphine, amitriptyline, prazosin, clonidine and a NO donor, SIN-1, in the presence of MG were found to be significantly anti-allodynic. A long-term anti-allodynic effect at 7 and 13 days post-I/R after repeated oral doses of MG (50 and 100 mg/kg) was also observed. Further, MG decreased spinal and muscle interleukin-1β concentration and restored muscle redox status. These results indicate that MG has a transient and long-term anti-allodynic effect in CPIP rats that appears to be at least partially attributable to the opioid and α2 adrenergic receptors. Additionally, its anti-inflammatory and antioxidant mechanisms could also be implicated in this effect. The association of MG with sub-effective doses of these drugs enhances the anti-allodynic effect; however, an isobolographic analysis should be performed to define a functional interaction between them. These findings suggest the possible clinical use of MG in the treatment of CRPS-I in both early sympathetically maintained pain and long-term sympathetically independent pain.