"EXPLORING DIPHENHYDRAMINE THERAPEUTIC POTENTIAL IN THE MANAGEMENT OF PARKINSON'S DISEASE: A REVIEW"

Samenvatting

Parkinson’s Disease(PD) is a clinical syndrome characterised by movement disorders, muscle rigidity, tremors, and postural instability caused by deficiency of dopamine in the brain. Parkinson disease is age-related progressive neurodegenerative disease and is pathophysiologicallycharacterised by loss of dopaminergic neurons in the substantianigra para compacta(SNpc) in the basal ganglia part of the brain. Biochemically, it leads to oxidative stress, glutathione depletion, aggregation of alpha-synuclien, expression of lysosomal enzymes, which causes neuroinflammation and aggravates the symptoms of PD. Therapeutic interventions used for treatment of parkinson’s disease patients are mostly includes Levodopa which is precursor of dopamine and restore dopaminergic tone in stratium, other includes monoamine-oxidase inhibitors that decrease metabolism of dopamine in neurons, Dopamine agonists, Catechol-o-transferase inhibitors, antioxidants,etc( DeMaagd and Philip, 2015; Zahoor et al., 2018). Evidences from recent studies suggests that Diphenhydramine, a Histamine-1 receptor antagonists, shows neuroprotective effects in brain’s diseases. One clinical study supports that diphenhydramine reduces tremors in Parkinson’s disease patient, due to the anticholinergic effect of drug, it reduces the level of acetylcholine in neostraital-mediated neurotransmission, by which it relieves the motor-symptoms like tremors(Gonzalez, 2009; Nicholson et al., 2002). One another experimental research on rats supports that diphenhydramine reduces the level of inflammatory cytokines like TNF-alpha, Interleukins-1,6 and also reduces the level of lysosoal enzymes, fibrogenprotien markers and c-reactive protien which helps in reducing inflammation and it also increases the level of antioxidant enzymes. Thus, by this it possesses anti-inflammatory action and antioxidant action(Wang et al., 2019; Dias et al., 2013). One another experimental research on rats provides evidences that diphenhydramine blocks the mitochondrial apoptosis by downregulation of Bax-gene, caspase-3 and by upregulation of Bcl2-gene, which in results protects mitochondria from dysfunction, thus, results in decreasing the level of ROS in neurons. It also reduces the level of inflammatory cytokines like TNF-alpha, Interleukins-1beta, which helps in lowering the level of neuroinflammtion, hence, diphenhydramine provides antioxidant and anti-inflammatory action in Traumatic brain injury rat model(Pan et al., 2019; Dias et al., 2013).

One study also reported that Diphenhydramine possesses local anaesthetic action. 1% solution of Diphenhydramine is founded to be safe, cost-effective and efficacous and provides local anaesthetic action in surgical procedures in patients which have allergy to “caine” local anaesthesia. Thus, Diphenhydramine is also used as alternative to “caine” local anaesthetic in surgical procedures in Parkinson’s disease patients(Pavlidakey et al., 2009). One another study reported that diphenhydramine has sedative action, so, founded effective in treatment of insomania in Pd. Diphenhydramine also blocks the reuptake of serotonin by antagonising the 5-HT reuptake transporter(SERT). Thus, by this action it is also used as anti-depressent drug in treatment of symptoms like depression in Pd(Gupta and Shukla, 2021; Pathy, 2018). Because diphenhydramine has anticholinergic action by antagonising the muscranic cholinergic receptors, thus, inhibits the acetylcholine from binding in synaptic cleft, by this, it helps in alleviating tremors in PD and also used in treatment of motion sickness in Patients(DeMaagd and Philip, 2015; Pathy, 2018).

Hence, above studies supports that the diphenhydramine reduces tremors and possesses antioxidant and anti-inflammatory action, thus, encouraged by above studies we intended to study the effect of diphenhydramine on experimental induced Parkinson’s disease in rats for better therapeutic effect of it in the diagnosis and treatment of PD, so, that if it provides the neuroprotective effects in PD, it also helps in improving the quality of life of various parkinson’s disease patients.