Haloperidol

Haloperidol is an antipsychotic drug that has similar actions to the antipsychotic medicine phenothiazine [1].

Haloperidol has been reported to play a role as an inverse agonist of dopamine. In addition, Haloperidol has been found to be highlt potent neuroleptic by relieving nervous through the depression of nerve function. Besides, Haloperidol has shown about 50-fold potency than chiorpromazine, the other antipsychotic drug. Haloperidol has shown beneficial effects in the treatment of delusions and hallucinations. These effects are mainly achieved through blockage of dopamine receptors in the mesocortex and limbic system. Haloperidol has been revealed to prevent the effects of dopamine in the nigrostriatal pathways, which probably explains the associated side effects such as akathisia and dystonias[1].

References:
[1] Dr Ananya Mandal, MD .Haloperidol Pharmacology.

Pharmacological assessments of potent A2A receptor antagonist IDPU (1-(7-imino-3-propyl-2,3-dihydrothiazolo[4,5-d]pyrimidin-6(7H)-yl)urea) in rodent model of haloperidol induced Parkinson like symptoms.[Pubmed:28336342]

Neurosci Lett. 2017 Apr 24;647:53-60.

A2A receptor antagonists emerged as potential candidate for management of Parkinson's disease. Earlier we had reported the therapeutic potential of 1-(7-imino-3-propyl-2,3-dihydrothiazolo[4,5-d]pyrimidin-6(7H)-yl) urea (IDPU) as A2A receptor antagonist. Herein, we have investigated the effect of IDPU in attenuation of Haloperidol induced Parkinson like symptoms in rats. It has successfully restored hypo-locomotion induced by Haloperidol and NECA. IDPU also displayed protective effect against oxidative stress induced by chronic Haloperidol treatment in rats. The antidepressant activity of IDPU was determined in mice showed that it imperatively reduced depression like symptoms in well-established depression models viz. TST and FST. Additionally, IDPU was found to be a safe and non-toxic chemical entity in acute, sub-acute and neurotoxicity studies. In silico study of IDPU showed acceptable physicochemical parameters and in vitro screening exhibited satisfactory metabolic stability. This study clearly indicates that A2A receptor antagonist IDPU is able to ameliorate Parkinsonian symptoms without exerting any significant toxicity.

Behavioral and neurochemical effects of alpha lipoic acid associated with omega-3 in tardive dyskinesia induced by chronic haloperidol in rats.[Pubmed:28329449]

Can J Physiol Pharmacol. 2017 Jul;95(7):837-843.

Tardive dyskinesia (TD) is characterized by involuntary movements of the lower portion of the face being related to typical antipsychotic therapy. TD is associated with the oxidative imbalance in the basal ganglia. Lipoic acid (LA) and omega-3 (omega-3) are antioxidants acting as enzyme cofactors, regenerating antioxidant enzymes. This study aimed to investigate behavioral and neurochemical effects of supplementation with LA (100 mg/kg) and omega-3 (1 g/kg) in the treatment of TD induced by chronic use of Haloperidol (HAL) (1 mg/kg) in rats. Wistar male rats were used, weighing between 180-200 g. The animals were treated chronically (31 days) with LA alone or associated with HAL or omega-3. Motor behavior was assessed by open-field test, the catalepsy test, and evaluation of orofacial dyskinesia. Oxidative stress was accessed by determination of lipid peroxidation and concentration of nitrite. LA and omega-3 alone or associated caused an improvement in motor performance by increasing locomotor activity in the open-field test and decreased the permanence time on the bar in the catalepsy test and decreased the orofacial dyskinesia. LA and omega-3 showed antioxidant effects, decreasing lipid peroxidation and nitrite levels. Thus, the use of LA associated with omega-3 reduced the extrapyramidal effects produced by chronic use of HAL.

Antioxidant effects of rice bran oil mitigate repeated haloperidol-induced tardive dyskinesia in male rats.[Pubmed:28374238]

Metab Brain Dis. 2017 Aug;32(4):1099-1107.

Tardive dyskinesia (TD) is associated with the use of antipsychotic drugs such as D2 antagonist Haloperidol (HP). The chronic use of HP is involved in the causation of free radicals and/or oxidative stress. In view of the nootropic, anti-anxiety, anti-inflammatory-like effects of rice bran oil (RBO) in a variety of investigations, we assessed the protective properties of RBO on HP-induced TD and neurochemical alteration. Rats treated with HP orally at a dose of 0.2 mg/kg/day for a period of 5 weeks developed VCMs which increased progressively as the treatment continued for 5 weeks. Co-administration of RBO by oral tubes at a dose of 0.4 ml/day prevented the induction of HP-induced VCMs. Repeated administration of HP increases the turnover of dopamine metabolism in the striatum. Conversely animals treated with HP + RBO decrease the metabolism of DA than water + HP treated animals. Striatal, malondieldehyde (MDA), hydrogen peroxide (H2O2) and antioxidant enzyme superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were also determined. It is suggested that beneficial role of RBO in attenuation of HP-induced TD. The results therefore recommended that supplementation of RBO may be useful in the HP-induced TD. The findings have also potential implication in the treatment of schizophrenia and motor disorders.