VU0152100 (10, 30, 56.6 mg/kg; ip; single) counteracts hypermotility brought on by amphetamines [1]. VU0152100 (10, 30, 56.6 mg/kg; ip; single) counteracts hypermotility brought on by amphetamines [1]. In the nucleus accumbens and caudate-putamen, VU0152100 reverses amphetamine-induced elevations in extracellular dopamine levels [1].

Animal/Disease Models: Adult male SD (SD (Sprague-Dawley)) rat (250-275 g; amphetamine-induced hyperlocomotion model) [1].
Doses: 10, 30, 56.6 mg/kg
Route of Administration: intraperitoneal (ip) injection; Single (pre-treatment)
Experimental Results: Powerful dose-dependent reversal of amphetamine-induced hyperkinesis.

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Animal/Disease Models: Adult male SD (SD (Sprague-Dawley)) rat (250-275 g; amphetamine induction) [1].
Doses: 10, 30, 56.6 mg/kg
Route of Administration: intraperitoneal (ip) injection; Single (pre-treatment)
Experimental Results: Blocked amphetamine-induced disruption of prepulse inhibition. Dose-dependently reversed the disruptive effects of amphetamine on the acquisition of context-dependent fear.

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Multiple detailed animal protocols were used to evaluate VU0152100.

1. **Drug Formulation:** VU0152100 was dissolved in 10% Tween 80 plus double deionized water and administered i.p. in a volume of 2 mL/kg. [1]
2. **Amphetamine-Induced Hyperlocomotion (Rats):** Male Sprague-Dawley rats were habituated to open field chambers for 30 min, then pre-treated with vehicle or VU0152100 (3-56.6 mg/kg, i.p.). Thirty minutes later, they received amphetamine (1 mg/kg, s.c.) or vehicle and were monitored for another 60 min. [1]
3. **Amphetamine-Induced Hyperlocomotion (Mice):** Wild-type and M4 KO mice were habituated for 90 min, then injected with vehicle or VU0152100 (30 mg/kg, i.p.). Thirty minutes later, amphetamine (1.8 mg/kg, i.p.) was administered, and activity was monitored for 120 min. [1]
4. **Prepulse Inhibition (PPI):** Rats were pre-treated with vehicle or VU0152100 (3-30 mg/kg, i.p.) for 20 min, then injected with amphetamine (3 mg/kg, s.c.). After 10 min, they were placed in startle chambers for a 20-min session with randomized presentations of various trial types (pulse alone, prepulse alone, prepulse+pulse). [1]
5. **Contextual Fear Conditioning:** Rats were handled and injected with saline for 2 days. On conditioning day, they received vehicle or VU0152100 (10-56.6 mg/kg, i.p.), followed 15 min later by vehicle or amphetamine (4.8 mg/kg, s.c.). After another 15 min, they were placed in chambers for a 7-min conditioning session (four footshocks). Twenty-four hours later, freezing behavior was assessed for 7 min in the same context without shocks. [1]
6. **In Vivo Microdialysis:** Guide cannulae were implanted into the nucleus accumbens or caudate-putamen of rats. After recovery, microdialysis probes were inserted. On the experiment day, rats were placed in open field chambers. After baseline collection, they received vehicle or VU0152100 (56.6 mg/kg, i.p.), followed 30 min later by vehicle or amphetamine (1 mg/kg, s.c.). Dialysate samples were collected every 15 min for 120 min and analyzed for dopamine and its metabolites by HPLC-ECD. [1]
7. **Pharmacological MRI (phMRI):** Anesthetized, ventilated rats with pre-implanted jugular and i.p. catheters were placed in a 9.4T MRI scanner. After iron oxide nanoparticle injection for contrast, a 15-min baseline was collected. Rats then received vehicle or VU0152100 (56.6 mg/kg, i.p.), followed 15 min later by vehicle or amphetamine (1 mg/kg, i.p.), with 45 min of continuous acquisition. Data were processed to calculate fractional cerebral blood volume (CBV) changes. [1]
8. **Catalepsy Test:** Rats received vehicle, VU0152100 (30-100 mg/kg, i.p.), or haloperidol (1.5 mg/kg, i.p.). Catalepsy was assessed at 30, 60, 120, and 240 min post-treatment by placing the forepaws on a bar and measuring the time to remove them. [1]
9. **Modified Irwin Test:** Rats received vehicle, VU0152100 (56.6 mg/kg, i.p.), or oxotremorine (1 mg/kg, s.c.). Autonomic and somatosensory functions (salivation, lacrimation, piloerection, respiratory rate) and body temperature were assessed at 5, 15, 60, 120, and 240 min post-injection. [1]

[1]. Antipsychotic drug-like effects of the selective M4 muscarinic acetylcholine receptor positive allosteric modulator VU0152100. Neuropsychopharmacology. 2014 Jun;39(7):1578-93.

[2]. Centrally active allosteric potentiators of the M4 muscarinic acetylcholine receptor reverse amphetamine-induced hyperlocomotor activity in rats. J Pharmacol Exp Ther. 2008 Dec;327(3):941-53.

C18H19N3O2S

341.429

341.12

409351-28-6

864492

Light yellow to khaki solid powder

4.406

2

5

4

24

442

0

MDNWGCQSCGNTKH-UHFFFAOYSA-N

InChI=1S/C18H19N3O2S/c1-10-8-11(2)21-18-14(10)15(19)16(24-18)17(22)20-9-12-4-6-13(23-3)7-5-12/h4-8H,9,19H2,1-3H3,(H,20,22)

3-amino-N-[(4-methoxyphenyl)methyl]-4,6-dimethylthieno[2,3-b]pyridine-2-carboxamide

VU-152100VU-0152100VU 0152100VU0152100VU152100VU 152100

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ≥ 50 mg/mL (~146.44 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (7.32 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (7.32 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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 (Please use freshly prepared in vivo formulations for optimal results.)