Antipsychotics behavioral effects

Migler BM, Warawa EJ, Malik JB. Seroquel behavioral effects in conventional and novel tests for atypical antipsychotic drug. Psychopharmacology 1993 112 299-307. 

Tourette s syndrome (TS) is a chronic neurological disorder characterized by motor tics, involuntary verbalizations, and obsessive-compulsive behaviors. The current treatment lends itself to the use of antipsychotic agents. However, these treatments are only effective in about 70% of the treated population.84-85 Nicotine potentiates the behavioral effects of antipsychotics in a number of animal models.86 Clinical trials are under way involving patients receiving both nicotine and antipsychotic agents and appear to be promising.87 To date, there have been no studies mentioning the use of lobeline in TS. 

No article was found reporting anxiolytic activity of phenolic acids. However, the anxiolytic activity of the alkaloids is known. Anxiolytic properties may be a crucial feature of newer antipsychotics associated with the improvement of negative symptoms in schizophrenic patients. The indole alkaloid alstonine acts as an atypical antipsychotic in behavioral models, but differs in its dopamine and serotonin binding profile [310]. Behavioral effects of psychollatine, a glycoside indole monoterpene alkaloid isolated from Psychotria umbellate Thoim., was investigated in models of anxiety, depression, memory, tremor, and... 

BEHAVIORAL EFFECTS A number of effects in animal behavioral models have been used to predict the efficacy or potential adverse effects of antipsychotic agents. Despite their widespread use, these paradigms generally have not provided important insights into the basis for clinical antipsychotic effects. 

Toxicology LD50 (oral, rat) 23,160 mg/kg, (IP, rat) > 1 g/kg, (IV, mouse) 1530 mg/kg harmful by inh., skin contact danger of cumulative effects may cause somnolence, muscle weakness, ataxia, convulsions, antipsychotic behavior, changes in liver/kidney/spleen wt. suspected carcinogen tumorigen mutagen TSCA listed... 

To date, clozapine remains the only drug with proven and superior efficacy in treatment-resistant patients, and it is currently the only drug approved for the treatment-resistant schizophrenic. Studies have shown a response of approximately 30% to 50% in these well-defined treatment-resistant patients. Clinical trials have consistently found clozapine to be superior to traditional antipsychotics for treatment-refractory patients, and it is efficacious even after nonresponse to other SGAs and in partially responsive patients. It is often rapidly effective even in those who have had a poor response to other medication for years. Recent studies have demonstrated that it has a beneficial effect for aggression and suicidality, which led to the Food and Drug Administration (FDA) approval for the treatment of suicidal behavior in people with psychosis.41... 

A role for the 5-HT7 receptor in the regulation of circadian rhythms has been implicated. As discussed above, 5-HT has been known for some time to induce phase shifts in behavioral circadian rhythms and modulate neuronal activity in the suprachiasmatic nucleus, the likely site of the mammalian circadian clock. The pharmacological characteristics of the effect of 5-HT on circadian rhythms are consistent with 5-HT7 receptor. Moreover, mRNA for the 5-HT7 receptor is found in the suprachiasmatic nucleus. There is also increasing evidence that the 5-HT7 receptor may play a role in psychiatric disorders. The regional distribution of 5-HT7 receptors in brain includes limbic areas and cortex. Atypical antipsychotics, such as clozapine and risperidone, and some antidepressants display high affinity for this receptor. In the periphery, 5-HT7 receptors havebeenshown to mediate relaxation of vascular smooth muscle. 

Klotz U, Avant GR, Hoyumpa Aet al. (1975) The effects of age and liver disease on the disposition and elimination of diazepam in adult man. J Clin Invest 55(2) 347-359 Kompoliti K and Goetz CG (1998) Neuropharmacology in the elderly. Neurol Clin 16(3) 599-610 Lanctot KL, Best TS, Mittmann N et al. (1998) Efficacy and safety of antipsychotics in behavioral disorders associated with dementia. J Clin Psychiatry 59(10) 550-561 Landi F, Onder G, Cesari M et al. (2005) Psychotropic medications and risk for falls among community-dwelling frail older people an observational study. J Gerontol A Biol Sci Med Sci 60(5) 622-626... 

Atypical antipsychotics may be helpful in managing the delusions and agitated behavior that can accompany dementia. These medications, include risperidone (Risperdal), quetiapine (Seroquel), ziprasidone (Geodon), aripiprazole (Abilify), and olanzapine (Zyprexa). All antipsychotics, typical and atypical, appear to increase the risk of death in patients with dementia and psychosis. This appears as a warning in the package inserts of the newer drugs. A prudent approach is to discuss this risk with the caregiver, use the lowest effective dose, and monitor for effectiveness. 

Antidepressants. In our experience, clinicians who are trying to manage the behavior of impulsive or aggressive patients too often overlook antidepressants. Antidepressants are often just as effective as anticonvulsants, antipsychotics, or benzodiazepines, especially when managing mild-to-moderate behavioral disturbances. Furthermore, antidepressants are generally easier to use and easier to tolerate than these alternatives. Once again, the SSRIs are best studied and so represent the favored first-line treatment for managing mild-to-moderate behavioral lability... 

Antipsychotics are drugs that have a specific sedative effect, and which improve the attitude and calm the behavior of psychotic patients. They do not cause dependence, and have been proposed for treating psychotic disorders (elimination of psychotic symptomatology— delirium, hallucinations) and schizophrenic patients. Drugs of this group are also frequently referred to as neuroleptics. The term major tranquilizer was used previously to distinguish them from minor tranquilizers/anxiolytics. 

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