Chlorpromazine nervous system

The first phenothiazine antipsychotic drugs, with chlorpromazine as the prototype, proved to have a wide variety of central nervous system, autonomic, and endocrine effects. Although efficacy of these drugs is primarily driven by D2-receptor blockade, their adverse actions were traced to blocking effects at a wide range of receptors including a adrenoceptors and muscarinic, Hi histaminic, and 5-HT2 receptors. 

Chlorpromazine Blockade of D2 receptors >> 5 2 receptors .-Receptor blockade (fluphenazine least) muscarinic (M)-receptor blockade (especially chlorpromazine and thioridazine) Hx-receptor blockade (chlorpromazine, thiothixene) t central nervous system (CNS) depression (sedation) t decreased seizure threshold t QT prolongation (thioridazine) Psychiatric schizophrenia (alleviate positive symptoms), bipolar disorder (manic phase) nonpsychiatric antiemesis, preoperative sedation (promethazine) pruritus Oral and parenteral forms, long half-lives with metabolism-dependent elimination Toxicity Extensions of effects on a - and M- receptors blockade of dopamine receptors may result in akathisia, dystonia, parkinsonian symptoms, tardivedyskinesia, and hyperprolactinemia... 

Chlorpromazine is a tranquilizing and antiemetic agent that may cause a number of side effects in the circulatory and nervous system and adverse effects on blood cells, skin, and the eye. Recent studies suggest a possible genotoxic activity for chlorpromazine, whereas it has been established that certain reactive metabolic intermediates are capable of binding with macromolecules including DNA. 

Kinross-Wright, V. (1955). Complications of chlorpromazine treatment. Diseases of the Nervous System, 16, 114-119. 

Wittrig, J., Coopwood, W. E. (1970). Lithium versus chlorpromazine for manics Initiative and productivity versus tranquilization and hospitalization. Diseases of the Nervous System, 31, 486-489. 

CIMETIDINE ANTIPSYCHOTICS -CHLORPROMAZINE, CLOZAPINE, HALOPERIDOL, OLANZAPINE, PERPHENAZINE, RISPERIDONE, SERTINDOLE, THIORIDAZINE, ZUCLOPENTHIXOL T plasma concentrations of these antipsychotics, with risk of associated adverse effects - Drugs Acting on the Nervous System, Antipsychotics Cimetidine is an inhibitor of CYP3A4 (sertindole, haloperidol, risperidone) CYP2D6 (chlorpromazine, risperidone, zudopenthixol, thioridazine, perphenazine) and CYP1A2 (clozapine, olanzapine, sertindole, haloperidol) Avoid concomitant use. Choose alternative acid suppression... 

Weiner WJ, Nausieda PA, Klawans HE. 1977. Effect of chlorpromazine on central nervous system concentrations of manganese, iron, and copper. Life Sci 20 1181-1186. 

Some of the physiological and biochemical actions of the barbiturates are similar to those exhibited by chlorpromazine and the other tranquillizers. Thus, the ascending reticular system is inhibited and there is evidence that barbiturates both stimulate and inhibit the hypothalamus. Their greater hypnotic action is probably due to the fact that, like all potential anaesthetics, they cause a general depression of the central nervous system. Like chlorpromazine, some barbiturates uncouple oxidative phosphorylation in vitro (p. 301). On the other hand, the barbiturates do not exert any antagonism in vitro towards histamine, 5-hydroxytryptamine, noradrenaline or acetylcholine nor is their adininistration accompanied by signs of extra-pyramidal stimulation. 

Psychiatrists have been using agents that are active in the central nervous system for hundreds of years. Stimulants and depressants were used to modify the mood and mental states of psychiatric patients. Amphetamine, sedatives, and hypnotics were used to stimulate or depress the mental states of patients. The synthesis of chlorpromazine by Charpentier ultimately caused a revolution in the treatment of schizophrenia, but who really discovered chlorpromazine Charpentier, who first synthesized the molecule in 1950 at Rhone-Poulenc s research laboratory Simon Courvoisier, who reported distinctive effects on animal behavior Henri Laborit, a French military surgeon who first noticed distinctive psychotropic effects in man or Pierre Deniker and Jean Delay, French psychiatrists who clearly outlined what has... 

Chlorpromazine prevents the entry of guanethidine into the adrenergic neurones of the sympathetie nervous system resulting in a loss of its blood pressure-lowering effeets. The other interacting antipsychotics probably have similar effeets. This is essentially the same mechanism of interaction as that seen with the trieyelie antidepressants , (p.888). 

The synthesis of chlorpromazine in the 1950s and the discovery soon thereafter of the drug s antipsychotic activity opened the modern era of biochemical investigations into the pharmacology of the central nervous system. One of the compounds prepared in the search for more effective antipsychotics was amitriptyline. (See Example 12.7)... 

Spironolactone, 1% eth Central nervous system drugs Apomorphine, 0.01% aq Chlorpromazine ... 

Casamenti et al. [1399] developed a method for screening 11 central nervous system drugs (phenobarbital, olanzapine, clozapine, risperidone, loxapine, haloperidol, imipramine, amitriptyline, fluoxetine, chlorpromazine, paroxetine) on a Cjg column (A = 230 nm) using a 20/11.7 water (0.4g tetramethylammonium perchlorate with 0.2 mL of 7% (m/m) HCIO4 to pH 2.8 with ammonia)/acetonitrile mobile phase. Keep in mind that perchlorates, when concentrated with some metals, are hazardous. Elution was complete in 35 min with good resolution for most compounds. Plots of the effects of mobile phase modifier level and percent acetonitrile on overall retention are presented. Linear ranges of 25-5000 ng/mL with detection limits of 10-250 ng/mL (analyte dependent) are reported. 

Nervous system A randomised, double-blind, crossover study of 12 healthy adults with risperidone demonstrated significant dose-dependent effects on balance control. This effect was observed at low doses with no clinically detectable extrapyramidal symptoms [249 -]. Pisa syndrome is a dystonia affecting cervical and lumbar musculature that has been reported with risperidone, paliperidone and chlorpromazine. A case is presented of a 31-year-old male with MS and FDD who developed Pisa syndrome after chronic risperidone treatment showed improvement with lurasidone, but recurrence with chlorpromazine [250 ]. Another case in a 23-year-old female with history of seizure due to periventricular focal nodular heterotopia occurring 12 months after risperidone treatment she was eventually managed on olanzapine and baclofen PSI ]. A case of persistent Parkinsonism in an 84-year-old male after 5 months of risperidone (2 mg per day) is reported [252 ]. Other dystonic phenomena reported with risperidone include dislocation of the temporomandibular joint [253 ]. 

---