13 research outputs found
Anti-depressant like activity of <i>N</i>-n-butyl-3-methoxyquinoxaline-2-carboxamide (<b>6o</b>) a 5-HT<sub>3 </sub>receptor antagonist
435-443<span style="font-size:11.0pt;font-family:
" times="" new="" roman";mso-fareast-font-family:"times="" roman";mso-bidi-font-family:="" mangal;mso-ansi-language:en-gb;mso-fareast-language:en-us;mso-bidi-language:="" hi"="" lang="EN-GB">The compound 6o (at 0.5, 1 and 2
mg/kg, ip) with optimum log P and pA2
value, was subjected to forced swim test (FST) and tail suspension test (TST).
The compound 6o significantly
reduced the duration of immobility in mice without affecting the base line
locomotion in actophotometer. Moreover, 6o
(2 mg/kg, ip), potentiated the 5-hydroxytryptophan
(5-HTP)-induced head twitch responses in mice and at 1 and 2 mg/kg, ip
antagonized the reserpine-induced hypothermia (RIH) in rats. In interaction
studies with various standard drugs/ligands using FST, <b style="mso-bidi-font-weight:
normal">6o (1 and 2 mg/kg, ip) potentiated the anti-depressant effect
fluoxetine (5 mg/kg, ip) and reversed the depressant effect of parthenolide (1
mg/kg, ip) by reducing the duration of immobility. Furthermore, 6o (1 and 2 mg/kg, ip) potentiated the
effect of bupropion (10 mg/kg, ip) in TST. The behavioural anomalies of the
olfactory bulbectomised (OBX) rats were augmented by chronic 6o (1 and 2 mg/kg) treatment as
observed from the modified open field test (parameters: ambulation, rearing,
fecal pellet). The results suggest that compound <b style="mso-bidi-font-weight:
normal">6o exhibited anti-depressant like effect in rodent models of
depression.</span
Anxiolytic-like effect of <i style="mso-bidi-font-style:normal">N</i>-n-butyl-3-methoxyquinoxaline-2-carboxamide (<b>6o</b>) in experimental mouse models of anxiety
510-514The present research was designed to
explore the anxiolytic-like activity of a novel 5-HT3 receptor antagonist (6o)
in
experimental mouse models of anxiety. The anxiolytic activity of '6o' at
(1 and 2 mg/kg, ip) was evaluated in mice by using a battery of behavioural
tests of anxiety such as elevated plus maze (EPM), light/dark aversion test,
hole board (HB) and open field test (OFT) with diazepam (2 mg/kg, ip) as a
standard anxiolytic. None of the tested doses of '6o' affected the base
line locomotion. Compound '6o' (2 mg/kg, ip) and diazepam (2mg/kg, ip)
significantly increased the percentage of both time spent and open arm entries
in the EPM test. Compound '6o' in (1 mg/kg, ip) dose was only able to
affect the percentage time spent in open arm significantly in the EPM test. In
the light and dark test, compound '6o' (2 mg/kg, ip) and diazepam
(2mg/kg, ip) significantly increased the total time spent in light compartment
as well as number of transitions from one compartment to other and number of
square crossed. Compound '6o' (1 and 2 mg/kg, ip) and diazepam (2 mg/kg,
ip) also significantly increased number of head dips and number of squares
crossed, whereas significantly decreased the head
dipping latency in HB test as compared to vehicle control group. In addition, '6o'
in both the doses and diazepam
(2mg/kg, ip) significantly increased the ambulation scores (squares crossed) in
OFT however, there was no significant effect of '6o' (1 and 2 mg/kg, ip)
and diazepam (2 mg/kg, ip) on rearing scores. To conclude compound '6o'
exhibited an
anxiolytic-like effect in animal models of anxiety
Anti-depressant-like activity of a novel serotonin type-3 (5-HT<sub>3</sub>) receptor antagonist in rodent models of depression
619-626N-Cyclohexyl-3-methoxyquinoxalin-2-carboxamide (QCM-13), a novel 5-HT3
antagonist identified from a series of compounds with higher pA2
(7.6) and good log P (2.91) value was screened in rodent models of depression
such as forced swim test (FST), tail suspension test (TST), interaction studies
with standard anti-depressants and confirmatory studies such as reversal of
parthenolide induced depression and reserpine induced hypothermia. In FST (2
and 4 mg/kg) and TST (2 and 4 mg/kg), QCM-13 significantly reduced the duration
of immobility in mice without affecting the base line locomotion. QCM-13 (2 and
4 mg/kg) was also found to have significant interaction with standard
anti-depressants (fluoxetine and bupropion in FST and TST respectively).
Further, reversal of parthenolide induced depression in mice and reserpine
induced hypothermia in rat models indicate the serotonergic influence of QCM-13
for anti-depressant potential