Haloperidol behavioral effects

Ridley, R.M. Baker, H.F. and Scraggs, P.R. The time course of the behavioral effects of amphetamine and their reversal by haloperidol in a primate species. Biol Psychiatry 14 753-765, 1979. 

The administration of low doses of PCP to rodents induces hyperactivity and stereotypy (Chen et al. 1959 ). The observation that neuroleptics such as chlorpromazine, haloperidol, and pimozide, and adrenolytics such as alpha-methyl paratyrosine antagonize these behavioral effects of PCP suggests that they are mediated by facilitation of central dopaminergic neurotransmission (Murray and Horita 1979). The actions of PCP on central dopaminergic neurotransmission may be similar to amphetamine. A dose of PCP (2.5 mg/kg) in rats, which has no effects when given alone, enhances the behavioral effects of 1 and 3 mg/kg of d-amphetamine (Balster and Chait 1978). PCP, like dopamine, has also been shown to suppress plasma prolactin (Bayorh et al. 1983). However, the firm establishment of an excl usive relationship between dopamine neuro-transmission and PCP effects is difficult because of the prominent interactions of this drug with other neurotransmitter systems. 

The close resemblance between schizophrenia and PCP-induced psychosis suggests that the behavioral effects produced by PCP might be useful as a model of psychosis. On this basis, most animal studies have examined the ability of various agents to modify PCP-induced hyperactivity and stereotypy. While some studies suggest that neuroleptics such as haloperidol (Castellani and Adams 1981 Garey et al. 1980), chlorpromazine, or clozapine (Freed et al. 

Cohen, I.L., Campbell, M., Posner, D., Small, A.D., Triebel, D., and Anderson, L.T. (1980) Behavioral effects of haloperidol in young autistic children an objective analysis using a within-subjects reversal design. / Am Acad Child Adolesc Psychiatry 19 665-677. 

Lin K-M, Lau J, Smith M, et al Comparison of alprazolam plasma levels and behavioral effects in normal Asian and Caucasian male volunteers. Psychopharmacology (Berl) 96 365-369,1988a Lin K-M, Poland RE, Lau JK, et al Haloperidol and prolactin concentrations in Asians and Caucasians. J Clin Psychopharmacol 8 195-201, 1988b... 

Haloperidol was discovered in the Janssen Laboratories in 1958 (280,315,320,322). It is a butyrophenone derivative and was pursued because of its ability to block the behavioral activating effects of amphetamine in rat models. The amphetamine models were used as screening tools, because symptoms observed in paranoid schizophrenia were noted to be similar to those that developed in chronic amphetamine abusers. The behavioral profile of haloperidol was qualitatively similar to that of CPZ, but haloperidol required up to 50-fold lower doses to exert the same behavioral effects as CPZ. Around this time, the term "major tranquilizer" began to be replaced by the term "neuroleptic." The compound was pursued very vigorously, and the initial clinical results were published only 10 months after the initial synthesis of the compound. Haloperidol is still one of the most widely pre-... 

Pillot, C., et al. Ciproxifan, a histamine Hs-receptor antagonist/inverse agonist, potentiates neurochemical and behavioral effects of haloperidol in the rat. J. Neurosci. 2002, 22, 7272-7280. 

Butvrophenones and related compounds - The butyrophenone was effective in the therapy of schizophrenics and caused only mild side effects it selectively blocked CAR (O.IX trifluperidol) in mice. AHR-2277 ( ) was more potent than chlorpromazine, but less potent than haloperidol, in suppressing CAR in mice and cats in doses below those producing obvious motor defects. A related compound AHR-1900 (9c) elicited neurolepticlike behavioral effects in mice, rats and squirrel monkeys. In a series of butyrophenones bearing unsaturated amino substituents, most potent CNS depressant activity in mice was noted with. Abbott-30360 (9e) combined neuroleptic properties with analgetic potency approximately equal to that of morphine. The most potent compound (lO) in a series of methyl-branched aminobutyrophenones was only weakly depressant in mlce. i... 

Behavioral and emotional effects In animal studies, ginseng does not prolong pentobarbital-induced sleep, nor does it affect spontaneous locomotion (Mitra et al. 1996). It does potentiate amphetamine-induced locomotion, but it reduces the stereotypy and lethality caused by amphetamine. Ginseng has analgesic effects, which are discussed at greater length in chapter 8. Catalepsy induced by haloperidol is potentiated by ginseng, while the hyperthermic effect of 5-HTP is attenuated. No antiseizure effects have been observed. 

For more than 40 years, Li+ has been used to treat mania. While it is relatively inert in individuals without a mood disorder, lithium carbonate is effective in 60 to 80% of all acute manic episodes within 5 to 21 days of beginning treatment. Because of its delayed onset of action in the manic patient, Li+ is often used in conjunction with low doses of high-potency anxiolytics (e.g., lo-razepam) and antipsychotics (e.g. haloperidol) to stabilize the behavior of the patient. Over time, increased therapeutic responses to Li+ allow for a gradual reduction in the amount of anxiolytic or neuroleptic required, so that eventually Li+ is the sole agent used to maintain control of the mood disturbance. 

Tourette s syndrome, a heterogeneous behavioral disorder associated with motor and vocal tics of variable form and severity, can be effectively treated with haloperidol. Antipsychotics can also be employed to control disturbed behavior in senile dementia or Alzheimer s disease, since they decrease confusion, agitation, and hyperactivity. Most of these drugs also exhibit a strong antiemetic effect and can sometimes be used clinically for this purpose. 

Anderson, L.T., Campbell, M., Adams, P., Small, A.M., Perry, R., and Shell, J. (1989) The effects of haloperidol on discrimination learning and behavioral symptoms in autistic children. J Autism Dev Disord 19 227-239. 

Tourette s syndrome is a well-studied condition, characterized by motor and phonic tics and by behavioral and psychological problems. While many neurotransmitters were implicated in the etiology of this disorder, it is now believed that the dopaminergic system and noradrenergic systems are involved. Two major clinical trials (Shapiro et ah, 1989 Sallee et al, 1997) indicated that haloperidol and pimozide reduced the severity of tics by 65%. However, these medications are associated with side effects (including possible cognitive impairment, sedation, dysphoria, and tardive dyskinesia) that may limit their effectiveness in children with MR. 

Several double-blind studies have demonstrated that typical agents are effective in decreasing problematic behaviors in children with DD. For example, haloperidol reduced anger, hyperactivity, and stereotypies (Campbell et al., 1979) in the dose range of 0.25-4 mg/day. Pimozide reduced problematic behaviors in children with PDD (Naruse et al., 1982). However, the possible long-term side effect of tardive dyskinesia remains a concern when using these agents. 

As researchers have pointed out, well-controlled, rigorous studies of the neuroleptics have been rare. One analysis of seven studies showed improvement of behavioral symptoms in 59% of patients, but there was also improvement in 41% of those taking placebo (sugar pill). Patients with psychosis but without signs of movement disorder are often started on 0.5-1 mg of haloperidol (Haldol), with a subsequent increase in the dosage, trading off between adverse side effects and benefits. 

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