Drotaverine Inhibitor of PDE4: Reverses the Streptozotocin Induced Alzheimer's Disease in Mice.

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disease associated with decline in memory and cognitive impairments. Phosphodiesterase IV (PDE4) protein, an intracellular cAMP levels regulator, when inhibited act as potent neuroprotective agents by virtue of ceasing the activity of Pro-inflammatory mediators. The complexity of AD etiology has ever since compelled the researchers to discover multifunctional compounds to combat the AD and neurodegeneration. The aim of this study was to probe into role of drotaverine a PDE4 inhibitor in the management of AD. Albino mice were divided into seven groups (n = 10). Group 1 control group received carboxy methyl cellulose (CMC 1 mL/kg), group II diseased group treated with streptozotocin (STZ 3 mg/kg) by intracerebroventricular (ICV) route, group III administered standard drug Piracetam 200 mg/kg and groups IV-VII were given drotaverine (10, 20, 40, and 80 mg/kg i/p respectively). Groups II-VII were given STZ (3 mg/kg, ICV) on 1st and 3rd day of treatment to induce AD. All the groups were given their respective treatments for 23 days. Improvement in learning and memory was evaluated by using behavioral tests like open field test, elevated plus maze test, Morris water maze test and passive avoidance test. Furthermore, brain levels of biochemical markers of oxidative stress, neurotransmitters, β-amyloid and tau protein were also measured. Drotaverine showed statistically significant dose dependent improvement in behavioral and biochemical markers of AD: the maximum response was achieved at a dose level of 80 mg/kg. The Study concluded that drotaverine ameliorates cognitive impairment and as well as exhibited modulated the brain levels of neurotransmitters.

• Authors: Samra Nazir, Fareeha Anwar, Uzma Saleem, Bashir Ahmad, Zohaib Raza, Maham Sanawar, Artta Ur Rehman, Tariq Ismail
• Journal: Neurochemical research (Neurochem Res) Vol. 46 Issue 7 Pg. 1814-1829 (Jul 2021) ISSN: 1573-6903 [Electronic] United States
• PMID: 33877499 (Publication Type: Journal Article)

Chemical References

• Neurotransmitter Agents
• Nootropic Agents
• Phosphodiesterase 4 Inhibitors
• Streptozocin
• drotaverin
• Papaverine
• Acetylcholinesterase

Topics

• Acetylcholinesterase (metabolism)
• Alzheimer Disease (chemically induced, drug therapy, metabolism)
• Animals
• Cognitive Dysfunction (chemically induced, drug therapy, metabolism)
• Female
• Learning (drug effects)
• Male
• Memory (drug effects)
• Mice
• Molecular Docking Simulation
• Morris Water Maze Test (drug effects)
• Neurotransmitter Agents (metabolism)
• Nootropic Agents (metabolism, therapeutic use)
• Open Field Test (drug effects)
• Papaverine (analogs & derivatives, metabolism, therapeutic use)
• Phosphodiesterase 4 Inhibitors (metabolism, therapeutic use)
• Protein Binding
• Streptozocin