J Basic Clin Physiol Pharmacol 2017; 28(2): 91–92
Editorial
Michal Horowitz
Antidepressant and anxiolytic-like, sedation and
hypnosis
DOI 10.1515/jbcpp-2017-0022
Under the article category “Behavior and Neuroprotec-
tion”, four articles are presented in this issue of the
Journal of Basic and Clinical Physiology and Pharmacology
exploring compounds affecting behavior in rat and mouse
experimental models. These studies tell us how hypothe-
sis-driven research can evolve into products that interact
with the serotonergic network and how can herbal prod-
ucts assist development of readily available neuroprotec-
tive agents.
The first two articles by Bhatt et al. [1] “Neuropharmaco-
logical and neurochemical evaluation of N-n-propyl-3-eth-
oxyquinoxaline-2-carboxamide (6n): a novel serotonergic
5-HT3 receptor antagonist for co-morbid antidepressant-
and anxiolytic-like potential using traumatic brain injury
model in rats” and [2] “Neuropharmacological evaluation
of a novel 5-HT3 receptor antagonist (4-benzylpiperazin-
1-yl) (3-methoxyquinoxalin-2-yl) methanone (6g) on lipopol-
ysaccharide-induced anxiety models in mice” evaluate the
properties of a novel drug 6n, a serotonergic 5-HT3 recep-
tor antagonist, as a potential antidepressant and anxiolytic
drug. Serotonin is the major neurotransmitter involved in
depression, and this compound was designed based on the
hypothesis of Rajkumar and Mahesh [3] that postsynaptic
5-HT3 receptor antagonists can facilitate specific binding
of 5-HT to other postsynaptic receptors such as 5-HT1B,
5-HT2A, and 5-HT2C, thereby aiding serotonergic transmis-
sion. Studies on 5-HT3A knockout mice further confirmed
the role of 5-HT3 receptor subtypes in depression and anxi-
ety-related behaviors [4]. Bhatt et al. use a battery of behav-
ioral tests to show the efficiency of 6n during exposure
to two stressors. In ­Lipopolysaccharide-induced anxiety
symptoms in mice, three behavioral paradigms were
applied to measure the impact of chronic treatment with
6n on anxiety attenuation and serotonin level. The com-
pound affected serotonin signaling, possibly by enhanc-
ing serotonergic transmission. The second model used by
Bhatt’s team was a traumatic brain injury rat model. Behav-
ioral experimental paradigms as well as assays measuring
serotonin, norepinephrine and brain-derived neurotrophic
factor levels confirmed the efficiency of 6n. This compound
has an optimum log P (2.52) and pA2 values (7.6) greater
than the standard 5-HT3 receptor antagonist, ondansetron
(pA2–6.9).
The third paper in this category is by Rajashree et al.
“Effect of Salacia reticulata W. and Clitoria ternatea L. on
the cognitive and behavioral enhancement in the strepto-
zotocin-induced young diabetic rats” [5]. The structural
and functional interaction of neurons with the surround-
ing vasculature is critical for proper function of the central
nervous system, including learning and memory [6]. Thus,
diabetic patients may suffer cognitive impairments which
affect quality of life. Using a plus maze, and a Morris water
maze, Rajashree et al. attempted to elucidate whether the
combination of two herbal formulas has a beneficial effect
on central cognitive pathologies caused by stretozotocin-
induced diabetes in young rats. The combined nootropic
treatment was found to be beneficial in young rats dur-
ing-onset diabetes, being preventive but not curative. The
authors hypothesize that the memory enhancement might
also be beneficial to those with deficiencies not related
to diabetes. The study is descriptive, and calls for future
mechanistic studies.
The last article published under the category “Behav-
ior and Neuroprotection” is by Md. Jakaria et  al. and
entitled “In vivo sedative and hypnotic activities of meth-
anol extract from the leaves of Jacquemontia paniculata
(Burm.f.) Hallier f. in Swiss Albino mice” [7]. Jacquemon-
tia is one of the superior genera belonging to Convol-
vulaceae, and includes approximately 120  species [8].
Jacquemontia pentantha leaves contain several flavonoid
species, with anti-oxidative, anti-hyperglycemic, and anti-
inflammatory activities. Psychotomimetic ergot alkaloids
have been also detected. It has neuro-pharmacological
impacts, as well as hypnotic and sedative activity and
the current study attempts to provide the scientific basis
of its use in traditional medicine. The authors employ
pharmacological behavioral tests and compare the crude
leaf extract (containing a mixture of carbohydrates, fla-
vonoids, phenols, tannins, saponins, phytosterols, fixed
oils, and glycosides) to conventional anxiolytic medica-
tions such as diazepam and thiopental sodium-induced
sleeping time determination test, which is used to test
92      Horowitz: Antidepressant and anxiolytic-like, sedation and hypnosis
sedation and hypnosis. The results of this investigation
prove that the J. pentantha leaf extract has sedative and
hypnotic activities. Future research may enable develop-
ment of herbal allopathic drugs to treat sleep disorders.
References
1. Bhatt S, Mahesh R, Jindal A, Devadoss T. Neuropharmacological
and neurochemical evaluation of N-n-propyl-3-ethoxyquinox-
aline-2-carboxamide (6n): a novel serotonergic 5-HT3 receptor
antagonist for co-morbid antidepressant- and anxiolytic-like
potential using traumatic brain injury model in rats. J Basic Clin
Physiol Pharmacol 2017;28:93–100.
2. Bhatt S, Mahesh R, Devadoss T, Jindal A. Neuropharmacological
evaluation of a novel 5-HT3 receptor antagonist (4-benzylpipera-
zin-1-yl)(3-methoxyquinoxalin-2-yl) methanone (6g) on lipopoly-
saccharide-induced anxiety models in mice. J Basic Clin Physiol
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reticulata W. and Clitoria ternatea L. on the cognitive and behav-
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Corresponding author: Michal Horowitz, Editor-in-Chief of the
Journal of Basic and Clinical Physiology and Pharmacology,
The Hebrew University, Environmental Physiology, POB 12272,
91120 Jerusalem, Israel, E-mail: m.horowitz@mail.huji.ac.il