Chemistry and Effects of Brainstem Acting Drugs

Saganuwan    Alhaji   Saganuwan
doi:10.2174/1871524919666190620164355
Abstract

Background: Brain is the most sensitive organ, whereas brainstem is the most important part of Central Nervous System (CNS). It connects the brain and the spinal cord. However, a myriad of drugs and chemicals affects CNS with severe resultant effects on the brainstem.
Methods: In view of this, a number of literature were assessed for information on the most sensitive part of brain, drugs and chemicals that act on the brainstem and clinical benefit and risk assessment of such drugs and chemicals.
Results: Findings have shown that brainstem regulates heartbeat, respiration and because it connects the brain and spinal cord, all the drugs that act on the spinal cord may overall affect the systems controlled by the spinal cord and brain. The message is sent and received by temporal lobe, occipital lobe, frontal lobe, parietal lobe and cerebellum.
Conclusion: Hence, the chemical functional groups of the brainstem and drugs acting on brainstem are complementary, and may produce either stimulation or depression of CNS.
Keywords: Brainstem, cerebropathy, death, drug, spinal cord, toxicant.
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Graphical Abstract

[1] 
Angeles-Fernandez-Gil, M.; Palacio-Bote, R OLeo- Barahona, M.; Mora-Encinas, J.P. Anatomy of brainstem: A gaze into the stem. Semin. Ultras CT MR,  2010, 31(3), 196-219.
[http://dx.doi.org/10.1053/j.sult.2010.03.006] 
[2] 
Resenbloom, M.J.; Pfefferbaum, A.; Sullnan, E.V. Structural brain alterations associated with alcoholism. Alcohol Healt. Res. World,  1995, 19, 266-272.
[3] 
O’Leary, D.S.; Block, R.I.; Koeppel, J.A.; Schultz, S.K.; Magnotta, V.A.; Ponto, L.B.; Watkins, G.L.; Hichwa, R.D. Effects of smoking marijuana on focal attention and brain blood flow. Hum. Psychopharmacol.,  2007, 22(3), 135-148.
[http://dx.doi.org/10.1002/hup.832] [PMID:  17397099] 
[4] 
Weitlauf, C.; Woodward, J.J. Ethanol selectively attenuates NMDAR-mediated synaptic transmission in the prefrontal cortex. Alcohol. Clin. Exp. Res.,  2008, 32(4), 690-698.
[http://dx.doi.org/10.1111/j.1530-0277.2008.00625.x] [PMID:  18341645] 
[5] 
Van Sickle, M.D.; Oland, L.D.; Ho, W.; Hillard, C.J.; Mackie, K.; Davison, J.S.; Sharkey, K.A. Cannabinoids inhibit emesis through CB1 receptors in the brainstem of the ferret. Gastroenterology,  2001, 121(4), 767-774.
[http://dx.doi.org/10.1053/gast.2001.28466] [PMID:  11606489] 
[6] 
Gili, T.; Saxena, N.; Diukova, A.; Murphy, K.; Hall, J.E.; Wise, R.G. The thalamus and brainstem act as key hubs in alterations of human brain network connectivity induced by mild propofol sedation. J. Neurosci.,  2013, 33(9), 4024-4031.
[http://dx.doi.org/10.1523/JNEUROSCI.3480-12.2013] [PMID:  23447611] 
[7] 
Shannon, R.; Baekey, D.M.; Morris, K.F.; Lindsey, B.G. Ventrolateral medullary respiratory network and a model of cough motor pattern generation. J. Appl. Physiol.,  1998, 84(6), 2020-2035.
[http://dx.doi.org/10.1152/jappl.1998.84.6.2020] [PMID:  9609797] 
[8] 
Bolser, D.C. Central mechanisms II: Pharmacology of brainstem pathways. Handb. Exp. Pharmacol.,  2009, 187(187), 203-217.
[http://dx.doi.org/10.1007/978-3-540-79842-2_10] [PMID:  18825342] 
[9] 
Bolser, D.C. Cough suppressant and pharmacologic protussive therapy: ACCP evidence-based clinical practice guidelines. Chest,  2006, 129(Suppl. 1), 238S-249S.
[http://dx.doi.org/10.1378/chest.129.1_suppl.238S] [PMID:  16428717] 
[10] 
Trepanier, L.A.  Maropitan: Novel antiemetic. In: Clin Brief, 2015,
  pp. 75-77.
[11] 
Diemunsch, P.; Grélot, L. Potential of substance P antagonists as antiemetics. Drugs,  2000, 60(3), 533-546.
[http://dx.doi.org/10.2165/00003495;200060030-00002] [PMID:  11030465] 
[12] 
Venkatraman, A.; Edlow, B.L.; Yang, M.H.I. The brainstem in emotion: A review. Front. Neuroanat.,  2017, 11(15), 1-12.
[13] 
Seeley, W.W.; Menon, V.; Schatzberg, A.F.; Keller, J.; Glover, G.H.; Kenna, H.; Reiss, A.L.; Greicius, M.D. Dissociable intrinsic connectivity networks for salience processing and executive control. J. Neurosci.,  2007, 27(9), 2349-2356.
[http://dx.doi.org/10.1523/JNEUROSCI.5587-06.2007] [PMID:  17329432] 
[14] 
Hermans, E.J.; Henckens, M.J.; Joëls, M.; Fernández, G. Dynamic adaptation of large-scale brain networks in response to acute stressors. Trends Neurosci.,  2014, 37(6), 304-314.
[http://dx.doi.org/10.1016/j.tins.2014.03.006] [PMID:  24766931] 
[15] 
Coenen, V.A.; Schlaepfer, T.E.; Maedler, B.; Panksepp, J. Cross-species affective functions of the medial forebrain bundle-implications for the treatment of affective pain and depression in humans. Neurosci. Biobehav. Rev.,  2011, 35(9), 1971-1981.
[http://dx.doi.org/10.1016/j.neubiorev.2010.12.009] [PMID:  21184778] 
[16] 
Tamrazi, B.; Almast, J. Your brain on drugs: Imaging of drug-related changes in the central nervous system. Radiographic,  2012, 32(3), 701-719.
[17] 
Feldberg, W.; Pyke, D.; Stubbs, W.A. Hyperglycaemia: Imitating Claude Bernard’s piqûre with drugs. J. Auton. Nerv. Syst.,  1985, 14(3), 213-228.
[http://dx.doi.org/10.1016/0165-1838(85)90111-0] [PMID:  2866209] 
[18] 
Cedernaes, J.; Bass, J. Decoding obesity in the brainstem. eLife,  2016, 5, 1-3.[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4861599/]
[19] 
Sumithran, P.; Prendergast, L.A.; Delbridge, E.; Purcell, K.; Shulkes, A.; Kriketos, A.; Proietto, J. Long-term persistence of hormone adaptations to weight loss. N. Engl. J. Med.,  2011, 365, 1597-1604.[https://www.ncbi.nlm.nih.gov/pubmed/22029981]
[20] 
D’Agostino, G.; Lyons, D.J.; Cristiano, C.; Burke, L.K.; Madara, J.C.; Campbell, J.N.; Garcia, A.P.; Land, B.B.; Lowell, B.B.; Dileone, R.J.; Heisler, L.K. Appetite controlled by a cholecystokinin nucleus of the solitary tract to hypothalamus neurocircuit. eLife,  2016, 5 e01225
[http://dx.doi.org/10.7554/eLife.12225] [PMID:  26974347] 
[21] 
Adan, R.A. Mechanisms underlying current and future anti-obesity drugs. Trends Neurosci.,  2013, 36(2), 133-140.
[http://dx.doi.org/10.1016/j.tins.2012.12.001] [PMID:  23312373] 
[22] 
Weich, T.M.; Tochetto, T.M.; Seligman, L. Brain stem evoked response audiometry of former drug users. Rev. Bras. Otorrinolaringol. (Engl. Ed.),  2012, 78(5), 90-96.
[PMID:  23108826] 
[23] 
Alemà, G.; Perria, L.; Rosadini, G.; Rossi, G.F.; Zattoni, J. Functional inactivation of the human brain stem related to the level of consciousness. Intravertebral injection of barbiturate. J. Neurosurg.,  1966, 24(3), 629-639.
[http://dx.doi.org/10.3171/jns.1966.24.3.0629] [PMID:  5906509] 
[24] 
de oliveira-Maul J.P.; de Carvalho, H.B.; Goto, D.M.; Maia, R.M.; Flo, G.; Barnabe, V.; Franco, D.R.; Benabou, S.; Pettacini, M.R.; Jacob-Filho, W.; Saldiva, P.H.N.; Lorenzi – Fillo, G.; Rubin, B.K.; Nakagawa, N.K. Aging, diabetes and hypertension are associated with decreased nasal mucocilliary clearance. Chest,  2013, 143(4), 1091-1097.
[PMID:  23100111] 
[25] 
Bestermann, W.; Houston, M.C.; Basile, J.; Egan, B.; Ferrario, C.M.; Lackland, D.; Hawkins, R.G.; Reed, J.; Rogers, P.; Wise, D.; Moore, M.A. Addressing the global cardiovascular risk of hypertension, dyslipidemia, diabetes mellitus, and the metabolic syndrome in the southeastern United States, part II: Treatment recommendations for management of the global cardiovascular risk of hypertension, dyslipidemia, diabetes mellitus, and the metabolic syndrome. Am. J. Med. Sci.,  2005, 329(6), 292-305.
[http://dx.doi.org/10.1097/00000441-200506000-00009] [PMID:  15958871] 
[26] 
Cooper, P.L.; Wahlqvist, M.L.; Simpson, R.W. Sucrose versus saccharin as an added sweetener in non-insulin-dependent diabetes: Short- and medium-term metabolic effects. Diabet. Med.,  1988, 5(7), 676-680.
[http://dx.doi.org/10.1111/j.1464-5491.1988.tb01079.x] [PMID:  2975554] 
[27] 
Berecek, K.H.; Barron, K.W.; Webb, R.L.; Brody, M.J. Vasopressin-central nervous system interactions in the development of DOCA hypertension. Hypertension,  1982, 4(3 Pt 2), 131-137.
[PMID:  7068203] 
[28] 
Enevoldson, T.P. Recreational drugs and their neurological consequences. J. Neurol. Neurosurg. Psychiatry,  2004, 75(Suppl. 3), iii9-iii15.
[PMID:  15316039] 
[29] 
Reis, D.J.; Fuxe, K. Brain norepinephrine: evidence that neuronal release is essential for sham rage behavior following brainstem transection in cat. Proc. Natl. Acad. Sci. USA,  1969, 64(1), 108-112.
[30] 
Aaapro, M.; Jordan, K.; Feyer, P. Pathophysiology of chemotherapy-induced nausea and vomiting; Springer Health Care: London, UK, 2015. 
[31] 
Singh, P.; Yoon, S.S.; Kuo, B. Nausea: A review of pathophysiology and therapeutics. Therap. Adv. Gastroenterol.,  2016, 9(1), 98-112.
[http://dx.doi.org/10.1177/1756283X15618131] [PMID:  26770271] 
[32] 
Kenward, H.; Pelligand, L.; Savary-Bataille, K.; Elliott, J. Nausea: Current knowledge of mechanisms, measurement and clinical impact. Vet. J.,  2015, 203(1), 36-43.
[http://dx.doi.org/10.1016/j.tvjl.2014.10.007] [PMID:  25453240] 
[33] 
Prieto, G.A. Abnormalities of dopamine D3 receptor signaling in the diseased brain. J. Cent. Nerv. Syst. Dis.,  2017, 9, 1-8.
[34] 
Ao, Y.; Go, V.L.W.; Toy, N.; Li, T.; Wang, Y.; Song, M.K.; Reeve, J.R., Jr; Liu, Y.; Yang, H. Brainstem thyrotropin-releasing hormone regulates food intake through vagal-dependent cholinergic stimulation of ghrelin secretion. Endocrinology,  2006, 147(12), 6004-6010.
[http://dx.doi.org/10.1210/en.2006-0820] [PMID:  16959836] 
[35] 
Julu, P.O.; Witt Engerström, I. Assessment of the maturity-related brainstem functions reveals the heterogeneous phenotypes and facilitates clinical management of Rett syndrome. Brain Dev.,  2005, 27(Suppl. 1), S43-S53.
[http://dx.doi.org/10.1016/j.braindev.2005.02.012] [PMID:  16182494] 
[36] 
Stein, P.S.G. Molecular, genetic, cellular, and network functions in the spinal cord and brainstem. Ann. N. Y. Acad. Sci.,  2013, 1279, 1-12.
[http://dx.doi.org/10.1111/nyas.12083] [PMID:  23530997] 
[37] 
Weise, D.; Adamidis, M.; Pizzolato, F.; Rumpf, J.J.; Fricke, C.; Classen, J. Assessment function with circular brand of vagus nerve stimulation in Parkinson’s disease. Plos One,  2015, 10(4) eol20786
[38] 
Sato, Y.M.; Sato, K.; Kamino, K. Optical approaches to embryonic development of neural functions in the brainstem. Prog. Neurobiol.,  2001, 63(2), 151-197.
[39] 
Popelar, J.; Groh, D.; Pelánová, J.; Canlon, B.; Syka, J. Age-related changes in cochlear and brainstem auditory functions in Fischer 344 rats. Neurobiol. Aging,  2006, 27(3), 490-500.
[http://dx.doi.org/10.1016/j.neurobiolaging.2005.03.001] [PMID:  16464658] 
[40] 
Jacquin, M.F.; Wiegand, M.R.; Renehan, W.E. Structure-function relationships in rat brain stem subnucleus interpolaris. VIII. Cortical inputs. J. Neurophysiol.,  1990, 64(1), 3-27.
[http://dx.doi.org/10.1152/jn.1990.64.1.3] [PMID:  1696961] 
[41] 
Reardon, S. Brainstem cells rejuvenate mice. Nature,  2017, 547, 369.
[42] 
Sanger, G.J.; Lee, K. Hormones of the gut-brain axis as targets for the treatment of upper gastrointestinal disorders. Nat. Rev. Drug Discov.,  2008, 7(3), 241-254.
[http://dx.doi.org/10.1038/nrd2444] [PMID:  18309313] 
[43] 
Trapp, S.; Richards, J.E. The gut hormone glucagon-like peptide-1 produced in brain: Is this physiologically relevant? Curr. Opin. Pharmacol.,  2013, 13(6), 964-969.
[http://dx.doi.org/10.1016/j.coph.2013.09.006] [PMID:  24075717] 
[44] 
Prabhu, P.; Banerjee, N.; Anil, A.; Abdulla, A. Role of sex hormones produced during menstrual cycle on brainstem encoding of speech stimulus. Eur. Arch. Otorhinolaryngol.,  2016, 273(11), 3647-3650.
[http://dx.doi.org/10.1007/s00405-016-4009-2] [PMID:  27015668] 
[45] 
Jafari, Z.; Ahmadi, P.; Ashayeri, H.; Zarandi, M.M. Cochlear responses and auditory brainstem response functions in adults with auditory neuropathy idye-synchrony and individuals with normal hearing. Audit. Vestibul. Res,  2007, 16(1), 36-46.
[46] 
Yang, Z.Y.; Chen, X.Q.; Sun, D.; Wei, D. Mortality in children with severe hand, foot and mouth disease in Guangxi, China. Indian Pediatr.,  2018, 55(2), 137-139.
[http://dx.doi.org/10.1007/s13312-018-1247-y] [PMID:  29242411] 
[47] 
Samy, K.L.; Osman, D.M.; Selim, M.H.; Mohamed, R.A. Communication skills, sensory integration functions and auditory brainstem: finding in a group of Egyptian children with autistic features. Egypt. J. Otolaryngol.,  2017, 28, 117-126.
[48] 
Wenthur, C.J.; Gentry, P.R.; Mathews, T.P.; Lindsley, C.W. Drugs for allosteric sites on receptors. Annu. Rev. Pharmacol. Toxicol.,  2014, 54, 165-184.
[http://dx.doi.org/10.1146/annurev-pharmtox-010611-134525] [PMID:  24111540] 
[49] 
de Natale, E.R.; Ginatempo, F.; Paulus, K.S.; Manca, A.; Mercante, B.; Pes, G.M.; Agnetti, V.; Tolu, E.; Deriu, F. Paired neurophysiological and clinical study of the brainstem at different stages of Parkinson’s Disease. Clin. Neurophysiol.,  2015, 126(10), 1871-1878.
[http://dx.doi.org/10.1016/j.clinph.2014.12.017] [PMID:  25622530] 
[50] 
Pettorossi, V.E.; Panichi, R.; Botti, F.M.; Biscarini, A.; Filippi, G.M.; Schieppati, M. Long-lasting effects of neck muscle vibration and contraction on self-motion perception of vestibular origin. Clin. Neurophysiol.,  2015, 126(10), 1886-1900.
[http://dx.doi.org/10.1016/j.clinph.2015.02.057] [PMID:  25812729] 
[51] 
Castellote, J.M.; Valls-Solé, J. The Start React effect in tasks requiring end-point accuracy. Clin. Neurophysiol.,  2015, 126(10), 1879-1885.
[http://dx.doi.org/10.1016/j.clinph.2015.01.028] [PMID:  25754260] 
[52] 
Valls-Solé, J. Neurophysiological studies of brainstem functions and reflexes: Publications from the Brainstem Society Meeting. Berlin, March 2014. Clin. Neurophysiol.,  2015, 126(10), 1869-1870.
[http://dx.doi.org/10.1016/j.clinph.2015.07.013] [PMID:  26238855] 
[53] 
Zheng, H.; Patterson, L.M.; Morrison, C.; Banfield, B.W.; Randall, J.A.; Browning, K.N.; Travagli, R.A.; Berthoud, H.R. Melanin concentrating hormone innervation of caudal brainstem areas involved in gastrointestinal functions and energy balance. Neuroscience,  2005, 135(2), 611-625.
[http://dx.doi.org/10.1016/j.neuroscience.2005.06.055] [PMID:  16111819] 
[54] 
Von Wussow, U.; Klaus, J.; Pagel, H. Is the renal production of erythropoietin controlled by the brainstem? Am. J. Endocrinol. Metab.,  2005, 289, 82-86.
[http://dx.doi.org/10.1152/ajpendo.00182.2004] 
[55] 
Hong, Y. Sympathovagal imbalance in type 2 diabetes-role of brainstem thyrotropin-releasing hormone.  Available at;
 Intech, dx.doi.or/10.5772/56541
[56] 
Travagli, R.A.; Hermann, G.E.; Browning, K.N.; Rogers, R.C. Brainstem circuits regulating gastric function. Annu. Rev. Physiol.,  2006, 68, 279-305.
[http://dx.doi.org/10.1146/annurev.physiol.68.040504.094635] [PMID:  16460274] 
[57] 
Zhan, Q.; Buchanan, G.F.; Motelow, J.E.; Andrews, J.; Vitkovskiy, P.; Chen, W.C.; Serout, F.; Gummadavelli, A.; Kundishora, A.; Furman, M.; Li, W.; Bo, X.; Richerson, G.B.; Blumenfeld, H. Impaired serotonergic brainstem function during and after seizures. J. Neurosci.,  2016, 36(9), 2711-2722.
[http://dx.doi.org/10.1523/JNEUROSCI.4331-15.2016] [PMID:  26937010] 
[58] 
Dobson, S.D.; Sherwood, C.C. Mosaic evolution of brainstem motor nuclei in catarrhine primates. Anat. Res. Int.,  2011, 2011236894
[http://dx.doi.org/10.1155/2011/236894] [PMID:  22567289] 
[59] 
Gross, L. Diverse toxic chemicals disrupt cell function through a common path. Plos Biol.,  2007, 5(2) e41
[http://dx.doi.org/10.1371/journal.pbio.0050041] [PMID:  20076658] 
[60] 
Mostil, M.G.; Fossal, P. Synthesis and preliminary biological evaluation of novel N-substituted 1-amino-3-methyl (phenyl)-1H-indozol-4-yloxy) propan-2-ols interesting as potential antiarrythmic, local anesthetic and analgesic agent. Arzn. Forsch Drug Res.,  2000, 50, 963-972.
[61] 
Kerzarea, D.R.; Khedekar, P.B. Indole derivatives acting on central nervous system-review. Pharmaceut. Sci. Biosci. Res.,  2016, 6(1), 144-156.
[62] 
Chandler, D.J. Evidence for a specialized role of the locus coeruleus noradrenergic system in cortical circuitries and behavioral operations. Brain Res., 2016, 1641(Pt B), 197-206., 
[http://dx.doi.org/10.1016/j.brainres.2015.11.022] [PMID: 
 26607255] 
[63] 
Mejias-Aponte, C.A. Specificity and impact of adrenergic projections to the midbrain dopamine system. Brain Res., 2016, 1641(Pt
 B), 258-273., 
[http://dx.doi.org/10.1016/j.brainres.2016.01.036] [PMID: 
 26820641] 
[64] 
Berridge, C.W.; Spencer, R.C. Differential cognitive actions of norepinephrine alpha2 and alpha1 receptor signaling in the prefrontal cortex. Brain Res., 2016, 1641(Pt B), 189-196, 
[http://dx.doi.org/10.1016/j.brainres.2015.11.024] [PMID: 
 26592951] 
[65] 
Bangasser, D.A.; Wiersielis, K.R.; Khantsis, S. Sex differences in the locus coeruleus-norepinephrine system and its regulation by stress.  Brain Res., 2016, 1641(Pt B), 177-188., 
[http://dx.doi.org/10.1016/j.brainres.2015.11.021] [PMID: 
 26607253] 
[66] 
Salgado, H.; Treviño, M.; Atzori, M.  Layer- and area-specific
 actions of norepinephrine on cortical synaptic transmission. Brain
 Res., 2016, 1641(Pt B), 163-176. 
[http://dx.doi.org/10.1016/j.brainres.2016.01.033] [PMID: 
 26820639] 
[67] 
Robertson, S.D.; Plummer, N.W.; Jensen, P. Uncovering diversity in the development of central noradrenergic neurons and their efferents. Brain Res., 2016, 1641(Pt B), 234-244., 
[http://dx.doi.org/10.1016/j.brainres.2015.11.023] [PMID: 
 26612521] 
[68] 
Zitnik, G.A. Control of arousal through neuropeptide afferents of the locus coeruleus. Brain Res., 2016, 1641(Pt B), 338-350., 
[http://dx.doi.org/10.1016/j.brainres.2015.12.010] [PMID: 26688115] 
[69] 
Pamphlett, R. Uptake of environmental toxicants by the locus ceruleus: a potential trigger for neurodegenerative, demyelinating and psychiatric disorders. Med. Hypotheses,  2014, 82(1), 97-104.
[http://dx.doi.org/10.1016/j.mehy.2013.11.016] [PMID:  24315447] 
[70] 
Liu, J.; Lewis, G. Environmental toxicity and poor cognitive outcomes in children and adults. J. Environ. Health,  2014, 76(6), 130-138.
[PMID:  24645424] 
[71] 
Wilding, B.C.; Curtis, K.; Welker-Hood, K.  Hazardous Chemicals
 in Health Care. A Snapshot of Chemicals on Doctors and Nurses,
 2017, pp. 1-39.
[72] 
Dailey, J.W. Sedative-hypnotic and anxiolytic drugs. Drug Affect. Cent. Nerv. Syst.,  2005, 1, 355-363.
[73] 
Mendelson, W.B. Basic mechanisms of sedative/hypnotics.In: Neuropsychopharmacology; The Fifth Generation of Progress; Davis, K.L.; Chaney, D.; Coyle, J.T.; Nemeroffi, C., Eds.; Wiley & Sons: New York, 2002, pp. 1923-1929.
[74] 
Pawson, P. Sedatives.In: Madison, J.; page, S.W.; Church, D.B. Small Animal Clinical Pharmacology; Elsevier: Amsterdam, 2008, p. 589.
[75] 
Ciraulo, D.A.; Oldham, M. Sedative hypnotics.In: The Effects of Drug Abuse on the Human Nervous System; Madras, B.; Kuhar, M., Eds.; Elsevier: Amsterdam, 2014, p. 624.
[http://dx.doi.org/10.1016/B978-0-12-418679-8.00016-2] 
[76] 
Quiqq, M. The normal waking electroencephalogram. MSc Thesis,
 University of Pearl’s, 2006.
[77] 
Hoffman, R.J.; Sharma, A.N. Withdrawal syndrome.In: Comprehensive Pediatric Hospital Medicine; Zoutis, L.B.; Chiang, V.W., Eds.; Elsevier: Amsterdam, 2007, p. 1349.
[78] 
Niizeki, K.; Saitoh, T. Association between phase coupling of respiratory sinus arrhythmia and slow wave brain activity during sleep. Front. Physiol.,  2018, 9, 1338.
[http://dx.doi.org/10.3389/fphys.2018.01338] [PMID:  30319446] 
[79] 
Raines, A. Hypnotics and anti-anxiety agents. Princip. Med. Biol.,  1997, 8, 623-640.
[http://dx.doi.org/10.1016/S1569-2582(97)80057-8] 
[80] 
Haynes, R.L.; Frelinger, A.L., III; Giles, E.K.; Goldstein, R.D.; Tran, H.; Kozakewich, H.P.; Haas, E.A.; Gerrits, A.J.; Mena, O.J.; Trachtenberg, F-L.; Paterson, D.S.; Berry, G.T.; Adeli, K.; Kinney, H.C.; Michelson, A.D. High serum serotonin in sudden infant death syndrome. Proc. Natl. Acad. Sci. USA,  2017, 114(29), 7695-7700.
[http://dx.doi.org/10.1073/pnas.1617374114] [PMID:  28674018] 
[81] 
Smith, C. Hippocampal abnormalities and sudden childhood death. Forensic Sci. Med. Pathol.,  2016, 12(2), 202-203.
[http://dx.doi.org/10.1007/s12024-016-9770-4] [PMID:  27026104] 
[82] 
Vester, M.E.M.; Bilo, R.A.; Karst, W.A.; Daams, J.G.; Duijst, W.L.J.M.; van Rijn, R.R. Subdural hematomas: Glutaric aciduria type 1 or abusive head trauma? A systematic review. Forensic Sci. Med. Pathol.,  2015, 11(3), 405-415.
[http://dx.doi.org/10.1007/s12024-015-9698-0] [PMID:  26219480] 
[83] 
Hefti, M.M.; Kinney, H.C.; Ryan, J.B.; Haas, E.A.; Chadwick, A.E.; Crandall, L.A.; Trachtenberg, F.L.; Armstrong, D.D.; Graife, M.; Kraus, H.F. Sudden unexpected death in early childhood: General observations in a series of 151 cases. Forensic Sci. Med. Pathol.,  2016, 12, 4-13.
[http://dx.doi.org/10.1007/s12024-015-9724-2] [PMID:  26782961] 
[84] 
Hunt, C.E.; Darnall, R.A.; McEntire, B.L.; Hyma, B.A. Assigning cause for sudden unexpected infant death. Forensic Sci. Med. Pathol.,  2015, 11(2), 283-288.
[http://dx.doi.org/10.1007/s12024-014-9650-8] [PMID:  25634430] 
[85] 
Ikeda, T.; Tani, N.; Aoki, Y.; Shida, A.; Morioka, F.; Oritani, S.; Ishikawa, T. Effects of postmortem positional changes on conjunctival petechiae. Forensic Sci. Med. Pathol.,  2019, 15(1), 13-22.
[http://dx.doi.org/10.1007/s12024-018-0032-5] [PMID:  30390281] 
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DOI https://dx.doi.org/10.2174/1871524919666190620164355	Print ISSN 1871-5249
Publisher Name Bentham Science Publisher	Online ISSN 1875-6166
Central Nervous System Agents in Medicinal Chemistry

Chemistry and Effects of Brainstem Acting Drugs

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