An Update on Assessment, Therapeutic Management, and Patents on Insomnia

Insomnia is an ordinary situation related to noticeable disability in function and quality of life, mental and actual sickness, and mishappenings. It represents more than 5.5 million appointments to family doctors every year. Nonetheless, the ratio of insomniacs who are treated keeps on being low, demonstrating the requirement for proceeding with advancement and dispersal of effective treatments. Accordingly, it becomes significant to provide a compelling treatment for clinical practice. It indicates a need for the determination of various critical viewpoints for the evaluation of insomnia along with various accessible alternatives for treatment. These alternatives incorporate both nonpharmacological therapy, specifically cognitive behavioural therapy for insomnia, and a number of pharmacological treatments like orexin antagonists, “z-drugs,” benzodiazepines, selective histamine H1 antagonists, nonselective antihistamines, melatonin receptor agonists, antipsychotics, antidepressants, and anticonvulsants. Besides in individuals whose insomnia is due to restless leg syndrome, depression/mood disorder, or/and circadian disturbance, there is insignificant proof favouring the effectiveness of different prescriptions for the treatment of insomnia though they are widely used. Other pharmacological agents producing sedation should be prescribed with care for insomnia therapy because of greater risk of next-day sleepiness along with known adverse effects and toxicities. This review is also aimed at providing an update on various patents on dosage forms containing drugs for insomnia therapy.

Histamine receptors in GtoPdb v.2021.3

Histamine receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Histamine Receptors [80, 173]) are activated by the endogenous ligand histamine. Marked species differences exist between histamine receptor orthologues [80]. The human and rat H3 receptor genes are subject to significant splice variance [12]. The potency order of histamine at histamine receptor subtypes is H3 = H4 > H2 > H1 [173]. Some agonists at the human H3 receptor display significant ligand bias [182]. Antagonists of all 4 histamine receptors have clinical uses: H1 antagonists for allergies (e.g. cetirizine), H2 antagonists for acid-reflux diseases (e.g. ranitidine), H3 antagonists for narcolepsy (e.g. pitolisant/WAKIX; Registered) and H4 antagonists for atopic dermatitis (e.g. adriforant; Phase IIa) [173] and vestibular neuritis (AUV) (SENS-111 (Seliforant, previously UR-63325), entered and completed vestibular neuritis (AUV) Phase IIa efficacy and safety trials, respectively) [216, 8].

Comprehensive treatment method for children with allergic rhinitis

Allergic rhinitis (AR) is a common childhood disease. At the same time, there is an underdiagnosis of this condition in the clinical practice and its significant impact on the life quality of the patient and his family. The article describes a modern stepwise approach in complex AR therapy in children. This approach involves the choice of drug therapy in accordance with the disease course. In this case, it is necessary, in particular, to take into account the clinically significant sensitization profile, the presence of concomitant allergic and non-allergic pathology, the patterns of the expected exposure of relevant allergens, the disease course severity, the patient’s age, response to therapy, etc. The current problems of conservative treatment are discussed. Information on the pharmacological drug groups for the AR treatment is presented: H1-antagonists, antileukotriene drugs, intranasal glucocorticosteroids. The main effects and the most common adverse events of their usage are considered. Practical issues of AR treatment tactics, relevant for pediatricians, allergists and otorhinolaryngologists, are highlighted. The prescription of drug combinations of different groups is substantiated, providing a simultaneous effect on different links of the pathogenetic process. The importance of elimination measures and allergen-specific immunotherapy is noted. KEYWORDS: allergic rhinitis, sensitization, H1-antagonists, leukotriene receptor antagonists, glucocorticosteroids, children. FOR CITATION: Asmanov A.I., Konyukova N.G., Pivneva N.D. et al. Comprehensive treatment method for children with allergic rhinitis. Russian Medical Inquiry. 2021;5(5):348–352 (in Russ.). DOI: 10.32364/2587-6821-2021-5-5-348-352.

Synthesis and Screening of Some Novel Thieno[2,3-d][1,2,3] triazine Derivatives as Non-sedative H1 Antihistaminics

Histamine receptor H1 antagonists are widely used as antihistamines for allergy conditions. The brain-penetrating antihistamines can cause sedation and some with poor-penetration do not cause sedation potential. In the present study, a new series of thieno[2,3-d][1,2,3]triazine derivatives 7a-e have been synthesized and screened for their H1 antihistaminic activity and sedation potential. Among all the screened compounds, compound 7b, 7c and 7d, show high H1 antihistaminic activity with IC50 value of 0.1 - 0.8 µM, which are comparable with that of the standard drug cetirizine. The sedative potential of the compounds was tested on albino mice using the photoactometer method. All the three compounds show less sedation potential than that of the standard drug diphenhydramine. In conclusion, the novel compounds appear with promising potential as non-sedating antihistamine agents.

Hypothesis of Biphasic SARS-Cov-2 Infections Manifesting as Hypersensitivity Pneumonitis

I hypothesize that SARS-Cov-2 presents as a biphasic disease, manifesting as hypersensitivity pneumonitis (HP) in phase 2, and often culminating in ARDS, sepsis, multi-organ failure, coagulatory dysfunction and a host of other decompensations. This report seeks to explain these symptoms and offers a potential prophylactic treatment. In absence of an effective vaccine or antiviral therapy to address acute viral replication (phase 1), treatments must focus on ameliorating phase 2 symptoms by properly addressing the root cause. I propose that phase 2 presentation of HP results from a local production of histamine; proportional and in response to viral load generated during phase 1 SARS-Cov-2 replication. Successful prevention of phase 2 symptoms would, therefore, likely involve prophylactic administration of H1-antagonists, H2-antagonists, and COX-inhibitors. Presentation of this hypothesis hopes for the initiation of a clinical trial to test for efficacy.

Histamine receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

Histamine receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Histamine Receptors [75, 163]) are activated by the endogenous ligand histamine. Marked species differences exist between histamine receptor orthologues [75]. The human and rat H3 receptor genes are subject to significant splice variance [12]. The potency order of histamine at histamine receptor subtypes is H3 = H4 > H2 > H1 [163]. Some agonists at the human H3 receptor display significant ligand bias [171]. Antagonists of all 4 histamine receptors have clinical uses: H1 antagonists for allergies (e.g. cetirizine), H2 antagonists for acid-reflux diseases (e.g. ranitidine), H3 antagonists for narcolepsy (e.g. pitolisant/WAKIX; Registered) and H4 antagonists for atopic dermatitis (e.g. ZPL-3893787; Phase IIa) [163] and vestibular neuritis (AUV) (SENS-111 (Seliforant, previously UR-63325), entered and completed vestibular neuritis (AUV) Phase IIa efficacy and safety trials, respectively) [205, 8].

Effects of chronic treatment with chlorpheniramine on anxiety and emotional memory in mice

Introduction: H1 receptors mediate actions in brain activity, and antihistamines such as chlorpheniramine (CPA) act as H1 antagonists. Objective: This study investigated the effects of chronic treatment with CPA on anxiety and emotional memory in mice in the elevated plus-maze (EPM). Method: Male Swiss albino mice received chronic treatment with saline or CPA for 15 days. After this, the test was performed on two consecutive days. In Trial 1, mice received an injection of saline or CPA, and 40 minutes later they were exposed to the EPM. Twenty-four hours later, the mice received injections again and were retested. Results: Results showed no effects on anxiety or locomotor activity. During trial 2, open-arm exploration diminished in mice treated only with CPA with a dosage of 16 mg/kg (ANOVA, SNK