Scopolamine

J Med Food. 2014 Oct;17(10):1049-56.

Rubus coreanus Miquel ameliorates scopolamine-induced memory impairments in ICR mice.[Pubmed: 25121635]

The present study investigated the effect of Rubus coreanus Miquel (RCM) on Scopolamine-induced memory impairments in ICR mice.
METHODS AND RESULTS:
Mice were orally administrated RCM for 4 weeks and Scopolamine was intraperitoneally injected into mice to induce memory impairment. RCM improved the Scopolamine-induced memory impairment in mice. The increase of acetylcholinesterase activity caused by Scopolamine was significantly attenuated by RCM treatment. RCM increased the levels of acetylcholine in the brain and serum of mice. The expression of choline acetyltransferase, phospho-cyclic AMP response element-binding protein, and phospho-extracellular signal-regulated kinase was significantly increased within the brain of mice treated with RCM. The brain antioxidant enzyme activity decreased by Scopolamine was increased by RCM.
CONCLUSIONS:
These results demonstrate that RCM exerts a memory-enhancing effect via the improvement of cholinergic function and the potentiated antioxidant activity in memory-impaired mice. The results suggest that RCM may be a useful agent for improving memory impairment.

Invert Neurosci. 2014 Sep;14(2):91-101.

Galantamine reverses scopolamine-induced behavioral alterations in Dugesia tigrina.[Pubmed: 24402079]

In planaria (Dugesia tigrina), Scopolamine, a nonselective muscarinic receptor antagonist, induced distinct behaviors of attenuated motility and C-like hyperactivity.
METHODS AND RESULTS:
Planarian locomotor velocity (pLMV) displayed a dose-dependent negative correlation with Scopolamine concentrations from 0.001 to 1.0 mM, and a further increase in Scopolamine concentration to 2.25 mM did not further decrease pLMV. Planarian hyperactivity counts was dose-dependently increased following pretreatment with Scopolamine concentrations from 0.001 to 0.5 mM and then decreased for Scopolamine concentrations ≥ 1 mM. Planarian learning and memory investigated using classical Pavlovian conditioning experiments demonstrated that Scopolamine (1 mM) negatively influenced associative learning indicated by a significant decrease in % positive behaviors from 86 % (control) to 14 % (1 mM Scopolamine) and similarly altered memory retention, which is indicated by a decrease in % positive behaviors from 69 % (control) to 27 % (1 mM Scopolamine). Galantamine demonstrated a complex behavior in planarian motility experiments since co-application of low concentrations of galantamine (0.001 and 0.01 mM) protected planaria against 1 mM Scopolamine-induced motility impairments; however, pLMV was significantly decreased when planaria were tested in the presence of 0.1 mM galantamine alone. Effects of co-treatment of Scopolamine and galantamine on memory retention in planaria via classical Pavlovian conditioning experiments showed that galantamine (0.01 mM) partially reversed Scopolamine (1 mM)-induced memory deficits in planaria as the % positive behaviors increased from 27 to 63 %.
CONCLUSIONS:
The results demonstrate, for the first time in planaria, Scopolamine's effects in causing learning and memory impairments and galantamine's ability in reversing Scopolamine-induced memory impairments.

J Affect Disord. 2014 Jun;162:39-42.

Antidepressant treatment history as a predictor of response to scopolamine: clinical implications.[Pubmed: 24767003]

The intravenous administration of Scopolamine produces rapid antidepressant effects. Generally, failing multiple previous antidepressant trials is associated with a poor prognosis for response to future medications. This study evaluated whether treatment history predicts antidepressant response to Scopolamine.
METHODS AND RESULTS:
Treatment resistant patients (2 failed medication trials) (n=31) and treatment naïve patients (no exposure to psychotropic medication) (n=31) with recurrent major depressive or bipolar disorder participated in a double-blind, placebo-controlled, crossover clinical trial. Following a placebo lead-in, participants randomly received P/S or S/P (P=3 placebo; S=3 Scopolamine (4ug/kg) sessions 3 to 5 days apart). The Montgomery-Asberg Depression Rating Scale (MADRS) was the primary outcome measure. A linear mixed model was used to examine the interaction between clinical response and treatment history, adjusting for baseline MADRS. Treatment resistant and treatment naïve subjects combined responded significantly to Scopolamine compared to placebo (F=15.06, p<0.001). Reduction in depressive symptoms was significant by the first post-Scopolamine session (F=42.75, p<0.001). A treatment history by Scopolamine session interaction (F=3.37, p=0.04) indicated treatment naïve subjects had lower MADRS scores than treatment resistant patients; this was significant after the second Scopolamine infusion (t=2.15, p=0.03). Post-hoc analysis: Also, we used a single regimen to administer Scopolamine, and smokers were excluded from the sample, limiting generalizability.
CONCLUSIONS:
Treatment naïve and treatment resistant patients showed improved clinical symptoms following Scopolamine, while those who were treatment naïve showed greater improvement. Scopolamine rapidly reduces symptoms in both treatment history groups, and demonstrates sustained improvement even in treatment resistant patients.

Afr J Tradit Complement Altern Med . 2017 Mar 1;14(3):136-141.

COGNITIVE-ENHANCING PROPERTIES OF MORINDA LUCIDA (RUBIACEAE) AND PELTOPHORUM PTEROCARPUM (FABACEAE) IN SCOPOLAMINE-INDUCED AMNESIC MICE[Pubmed: 28480424]

Abstract Background: Cognitive disorders associated with aging have been successfully managed by African traditional medical practitioners using various plants. This study evaluated the cognitive enhancing potentials of Morinda lucida (L) Rubiaceae and Peltophorum pterocarpum (DC) ex. K Heyne in Scopolamine induced amnesic animals. Materials and methods: The anti-amnesic activity of the ethyl acetate extracts of Morinda lucida and Peltophorum pterocarpum at doses of 4 mg/kg, 6 mg/kg and 8 mg/kg were assessed in Scopolamine induced amnesic mice using Morris water maze test model. Effect of the extracts on the histology of the hippocampus was also evaluated. Results: The ethyl acetate extract of Morinda lucida and Peltophorum pterocarpum ameliorated Scopolamine induced memory deficit in the animals under study. There was no effect of the extract on the histology of the hippocampus. However, there was an increase in the density of cells in the hippocampus of treated group as compared to the untreated. Conclusion: Morinda lucida and Peltophorum pterocarpum showed considerable enhancement of cognition in Scopolamine induced amnesic mice. Keywords: Hippocampus; Morinda lucida; Morris water maze; Peltophorum pterocarpum;

Indian J Pharmacol . Jan-Feb 2017;49(1):60-64.

Evaluation of neuroprotective effect of quercetin with donepezil in scopolamine-induced amnesia in rats[Pubmed: 28458424]

Abstract Objective: The objective of this study was to evaluate the neuroprotective effect of quercetin with donepezil in Scopolamine-induced amnesia in rats. Materials and methods: Five groups of adult male Wistar rats (12 months old) weighing 180-200 g (n = 6) were used. The normal control group received normal saline and test group animals were pretreated orally with quercetin (25 mg/kg), donepezil (3 mg/kg), and a combination of quercetin (25 mg/kg) with donepezil (3 mg/kg), respectively, dosed at every 24 h interval for 14 consecutive days, afterward amnesia was induced by Scopolamine (3 mg/kg) on the 14th day through intraperitoneal route. Cognitive performance was assessed by the Morris water maze, elevated plus maze, and passive avoidance paradigm. Acetylcholinesterase enzyme (AchE) level, biochemical markers such as lipid peroxidase (LPO), glutathione (GSH), β amyloid1-42level, and histopathological study of rat brain were estimated. Statistical analysis was done by one-way analysis of variance, followed by Dunnett's post hoc test. P ≥ 0.05 was considered statistically significant. Results: Pretreatment with quercetin, donepezil, and their combination showed a significant increase in escape latency, step-through latency, and decreased transfer latency in respective cognitive models of the Morris water maze, passive avoidance test, and elevated plus maze. Further coadministration significantly decreased AchE level, β amyloid1-42level as compared to individual therapy. Biochemical markers such as elevated GSH, decreased LPO were observed, and histopathological studies revealed the reversal of neuronal damage in the treatment group (P < 0.05) as compared to Scopolamine-treated control group. Conclusion: Pretreatment with quercetin potentiates the action of donepezil in Scopolamine-induced amnesia in rats. The improved cognitive memory could be due to the synergistic effect of the drugs by decreasing AchE level, β amyloid1-42level, and antioxidant action in rat brain. Keywords: Acetylcholinesterase enzyme; amnesia; donepezil; quercetin; Scopolamine.

J Pharmacol Exp Ther. 2014 Nov;351(2):448-56.

M1 and m2 muscarinic receptor subtypes regulate antidepressant-like effects of the rapidly acting antidepressant scopolamine.[Pubmed: 25187432]

Scopolamine produces rapid and significant symptom improvement in patients with depression, and most notably in patients who do not respond to current antidepressant treatments. Scopolamine is a nonselective muscarinic acetylcholine receptor antagonist, and it is not known which one or more of the five receptor subtypes in the muscarinic family are mediating these therapeutic effects.
METHODS AND RESULTS:
We used the mouse forced-swim test, an antidepressant detecting assay, in wild-type and transgenic mice in which each muscarinic receptor subtype had been genetically deleted to define the relevant receptor subtypes. Only the M1 and M2 knockout (KO) mice had a blunted response to Scopolamine in the forced-swim assay. In contrast, the effects of the tricyclic antidepressant imipramine were not significantly altered by gene deletion of any of the five muscarinic receptors. The muscarinic antagonists biperiden, pirenzepine, and VU0255035 (N-[3-oxo-3-[4-(4-pyridinyl)-1-piper azinyl]propyl]-2,1,3-benzothiadiazole-4-sulfonamide) with selectivity for M1 over M2 receptors also demonstrated activity in the forced-swim test, which was attenuated in M1 but not M2 receptor KO mice. An antagonist with selectivity of M2 over M1 receptors (SCH226206 [(2-amino-3-methyl-phenyl)-[4-[4-[[4-(3 chlorophenyl)sulfonylphenyl]methyl]-1-piperidyl]-1-piperidyl]methanone]) was also active in the forced-swim assay, and the effects were deleted in M2 (-/-) mice. Brain exposure and locomotor activity in the KO mice demonstrated that these behavioral effects of Scopolamine are pharmacodynamic in nature.
CONCLUSIONS:
These data establish muscarinic M1 and M2 receptors as sufficient to generate behavioral effects consistent with an antidepressant phenotype and therefore as potential targets in the antidepressant effects of Scopolamine.