4-Chloro-DL-phenylalanine

199.63

199.63

2805758

231-051-9

77370

DTXSID4045139

Crystals from methanol

2922499990

63.3

-0.48

White to almost white Powder

1.3±0.1 g/cm3

243-244 °C

339.5±32.0 °C at 760 mmHg

159.1±25.1 °C

1.590

H2O: slightly soluble

−20°C

6.09X10-9 mm Hg at 25 deg C (est)

Henry's Law constant = 8.93X10-11 atm-cu m/mol at 25 °C (est)

pKa1 = 2.08|pKa1 = 2.17 (carboxylic acid); pKa2 = 9.11(amine)

When heated to decomposition, it emits toxic fumes of NOx and Cl-|Hydroxyl radical reaction rate constant = 4.10X10-11 cu cm/molec-sec at 25 °C (est)

UN 2811 6.1/PG 3

3

25-43

36/37-45

AY4390010

T

Stable under normal temperatures and pressures.

P280-P301 + P310

H301-H317

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

|Danger|H301 (100%): Toxic if swallowed [Danger Acute toxicity, oral]|P261, P264, P270, P272, P280, P301+P310, P302+P352, P321, P330, P333+P313, P363, P405, and P501|Aggregated GHS information provided by 39 companies from 1 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|Aggregated GHS information provided by 39 companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

SRP: Wastewater from contaminant suppression, cleaning of protective clothing/equipment, or contaminated sites should be contained and evaluated for subject chemical or decomposition product concentrations. Concentrations shall be lower than applicable environmental discharge or disposal criteria. Alternatively, pretreatment and/or discharge to a POTW is acceptable only after review by the governing authority. Due consideration shall be given to remediation worker exposure (inhalation, dermal and ingestion) as well as fate during treatment, transfer and disposal. If it is not practicable to manage the chemical in this fashion, it must meet Hazardous Material Criteria for disposal.

This study examined the effects of serotonergic depletion and beta-adrenergic antagonism on performance in both visible platform and hidden platform versions of the water maze task. Male Long-Evans rats received systemic injections of p-chlorophenylalanine (500 mg/kg x 2) to deplete serotonin, or propranolol (20 or 40 mg/kg) to antagonize beta-adrenergic receptors. Some rats received treatments in combination. To separate strategies learning from spatial learning, half of the rats underwent Morris' water maze strategies pretraining before drug administration and spatial training. Individual depletion of serotonin or antagonism of beta-adrenergic receptors caused few or no impairments in either naive or pretrained rats in either version of the task. In contrast, combined depletion of serotonin and antagonism of beta-adrenergic receptors impaired naive rats in the visible platform task and impaired both naive and strategies-pretrained rats in the hidden platform task, and also caused sensorimotor impairments. ...|The goal of this study was to assess the interactive effects of chronic anabolic androgenic steroid (AAS) exposure and brain serotonin (5-hydroxytryptamine, 5-HT) depletion on behavior of pubertal male rats. Serotonin was depleted beginning on postnatal day 26 with parachlorophenylalanine (PCPA 100 mg/kg, every other day); controls received saline. At puberty (P40), half the PCPA-treated rats and half the saline-treated rats began treatment with testosterone (T, 5 mg/kg, 5 days/week). Behavioral measures included locomotion, irritability, copulation, partner preference, and aggression. Animals were tested for aggression in their home cage, both with and without physical provocation (mild tail pinch). Brain levels of 5-HT and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA), were determined using HPLC. PCPA significantly and substantially depleted 5-HT and 5-HIAA in all brain regions examined. Chronic T treatment significantly decreased 5-HT and 5-HIAA in certain brain areas, but to a much lesser extent than PCPA. Chronic exposure to PCPA alone significantly decreased locomotor activity and increased irritability but had no effect on sexual behavior, partner preference, or aggression. T alone had no effect on locomotion, irritability, or sexual behavior but increased partner preference and aggression. The most striking effect of combining T+PCPA was a significant increase in attack frequency as well as a significant decrease in the latency to attack, particularly following physical provocation. Based on these data, it can be speculated that pubertal AAS users with low central 5-HT may be especially prone to exhibit aggressive behavior.|...The dose-dependency and time-course of 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy")-nduced perturbations of cerebral glucose metabolism in freely moving rats /was investigated/ ... A single dose of MDMA (2-10-20 mg/kg iv) evoked a transient increase of interstitial glucose concentrations in striatum (139-223%) with rapid onset and of less than 2 hr duration, a concomitant but more prolonged lactate increase (>187%) at the highest MDMA dose and no significant depletions of striatal serotonin. Blood glucose and lactate levels were also transiently elevated (163 and 135%) at the highest MDMA doses. The blood glucose rises were significantly related to brain glucose and brain lactate changes. The metabolic perturbations in striatum and the hyperthermic response (+1.1 degrees C) following systemic MDMA treatment were entirely blocked in p-chlorophenylalanine pre-treated rats, indicating that these effects are mediated by endogenous serotonin.|This study examined the effect of both separate and combined depletion of brain somatostatin and serotonin on acquisition of the water maze (WM) task. Naive male Long-Evans rats received injections of p-chlorophenylalanine (PCPA; 500 mg/kg x 2) to deplete serotonin or cysteamine (90 or 200 mg/kg) to deplete somatostatin, or both treatments prior to spatial and reversal training in the water maze. Some rats first received Morris' nonspatial pretraining to train them in the behavioral strategies that are required for successful spatial place learning in this task, prior to drug treatment and spatial training. A detailed behavioral analysis indicated that somatostatin or serotonin depletion alone caused little or no impairment in naive animals. Depletion of both somatostatin and serotonin in naive rats impaired performance, with differences in the impairments that depended on the dose of cysteamine. Nonspatially pretrained rats were not impaired. Thus, neither somatostatin nor serotonin alone is crucial for the water maze task, but impairments occur if both somatostatin and serotonin are depleted in naive rats. The results indicate that some of the performance impairment was due to strategies impairment rather than a spatial place learning impairment. Depletion of both somatostatin and serotonin in naive rats produces results comparable to the spatial navigation deficits seen in some Alzheimer patients and suggests that combinations of antagonist treatments may better model this disorder than single antagonist treatments do.|For more Interactions (Complete) data for Fenclonine (11 total), please visit the HSDB record page.

Enzyme Inhibitors; Serotonin Antagonists|The clinical and biochemical features of a patient with flushing and severe diarrhea due to the carcinoid syndrome are described. The patient had a paradoxical response to the tryptophan hydroxylase inhibitor parachlorophenylalanine with complete abolition of flushing and no effect on the diarrhea. Treatment with this drug was limited by adverse effects. /Former/

... When the 5-HT concentration in sexually deficient men is sufficiently decreased with parachlorophenylalanine (PCPA) treatment and testosterone levels increased following its administration, a vivid sexual stimulation appears in about half of the untractable cases. Similar results are observed by substituting testosterone with monoamine oxydase inhibitor (MAOI) in PCPA-treated volunteers. . ...|A case is reported of a patient with carcinoid syndrome who developed a exogenous psychosis while under treatment with the serotonin-inhibitor p-chlorophenylalanine (PCPA). Partial symptoms similar to delirium and schizophrenia were exhibited.

Drugs that bind to but do not activate serotonin receptors, thereby blocking the actions of serotonin or SEROTONIN RECEPTOR AGONISTS. (See all compounds classified as Serotonin Antagonists.)|Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. (See all compounds classified as Enzyme Inhibitors.)

6- Fluorotryptophan (6-FT) and p-chlorophenylalanine (pCPA) were given orally to six (mean weight 5.3 kg) and five (mean weight 7.5 kg) monkeys respectively maintained on a controlled diet. Plasma amino acid concentrations were estimated using an amino acid analyser, and in the 6-FT studies free tryptophan was determined by equilibrium dialysis. At least 3 weeks separated each ingestion. The drugs were given in marzipan at 0900 hr on each occasion. With 10, 30 and 100 mg/kg 6-FT the mean peak plasma levels of 6-FT were 24, 58 and 145 n mole/mL respectively, and each peak was observed at 11.00 hours. With pCPA (10 and 100 mg/kg) the mean peak plasma levels of pCPA were 59 and 343 n mole/mL, and peaks were observed at 1100 and 1300 hr respectively. It was not possible to measure the plasma levels after ingestion of pCPA (1 mg/kg). The plasma half times for 6-FT and pCPA were about 3.5 and 10.5 hours. In control studies plasma concentrations of tryptophan increased during the day, and reached their maximum during the afternoon. The increases in the plasma concentration at 1300 and 1700 hr were highly significant (P<0.01). Oral ingestion of 6- FT (30 and 100 mg/kg) and pCPA (1 and 100 mg/kg) abolished the increase in plasma tryptophan during the day, and total plasma tryptophan concentrations were reduced compared with control levels at the same time of the day. The duration of each effect appeared to be related to the plasma half time of the inhibitor.

The plasma half times for 6-FT and pCPA were about 3.5 and 10.5 hours.

Administration of the specific serotonin depletor p-chlorophenylalanine to rats resulted in marked inhibition of tryptophan hydroxylase of the brain. The enzyme inhibition can be correlated with and is assumed to be responsible for brain serotonin depletion. Although p-chlorophenylalanine is a competitive inhibitor of tryptophan hydroxylase in vitro, it causes an irreversible inactivation of the enzyme in vivo. The findings also support the conclusion that tryptophan hydroxylation is the rate-limiting step in serotonin biosynthesis.

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/SIGNS AND SYMPTOMS/ Some of the mystery surrounding serotonin has been unraveled recently after the development of a means of selectively depriving the organism of this amine. Key aspects of recent advances include biochemical characterization of the first enzymatic step in tissue serotonin biosynthesis, that of tryptophan 5-hydroxylation; discovery of an inhibitor (para-chlorophenylalanine (PCPA)) of the reaction; and observations on the effects of serotonin deprival as produced by PCPA in man and animals. Control of diarrhea in the carcinoid syndrome by PCPA treatment indicates that the major target organ of circulating serotonin is the intestinal tract. Induction of psychiatric effects with high doses of PCPA, along with other evidence, is compatible with a serotonin-deficiency hypothesis of affective illness. Serotonin plays a role in sleep mechanisms, with PCPA suppressing and 5-hydroxytryptophan (serotonin precursor) restoring rapid eye movement sleep in man. Finally, animal data raise exciting possibilities of the involvement of brain serotonin in control of sexual behavior.|/CASE REPORTS/ Para-chlorophenylalanine is a potent depleter of tissue serotonin (5-hydroxytryptamine). Since 5-hydroxytryptamine may contribute to the pathogenesis of several aspects of the carcinoid syndrome, for 1 year ... a patient with this syndrome /was treated/ with para-chlorophenylalanine. A 59-year-old man developed chronic diarrhea, hepatomegaly, right-sided valvular heart lesion, and cutaneous flush. Exploratory abdominal examination showed ileal carcinoid tumor metastatic to liver and nodes. Urine 5-hydroxyindoleacetic acid and serum 5-hydroxytryptamine levels were abnormally high. Para-chlorophenylalanine treatment promptly reduced both levels to normal and halted the diarrhea. Chronic treatment with para-chlorophenylalanine controlled the production of 5-hydroxytryptamine and diarrhea but did not prevent tumor growth, flushing, or progression of cardiac lesions. /Former/|/CASE REPORTS/ Eighteen patients with severe symptoms of the carcinoid syndrome were assessed for hepatic embolisation. Four were too ill, and one had mild symptoms; thus 13 received a periembolisation regimen of cyproheptadine, fenclonine, aprotinin, methylprednisolone, tobramycin, flucloxacillin, and metronidazole. Embolization was not performed in one patient with an occluded portal vein and was unsatisfactory in two others, in one because she was moribund and in the other because the hepatic artery had been ligated. Dramatic improvement in symptoms occurred in the nine patients in whom embolisation was successfully carried out, with abolition of flushing, severe abdominal pain, and wheeze and reduction in diarrhea from 10.5 (SD 7.6) to 1.6 (0.9) stools/day. Urinary excretion of 5-hydroxyindole acetic acid fell from 1048 (716) to 289 (184) umol/24 hr (200 (137) to 55 (35) mg/24 hr). Complications included one death from septicaemia, a hepatic abscess requiring surgical drainage, abdominal pain in three patients, pleural effusion in two, and transient encephalopathy in one. Relief of symptoms lasted for one to 24 months, and second embolisation in two patients produced further remissions of four to six months. Five patients died, one to 40 months after embolisation, in four cases because of metastases or heart failure. ... /Former/|/CASE REPORTS/ Four of 46 patients with carcinoid tumors and the carcinoid syndrome developed severe life-threatening diarrhea. Although only 11% of the patients in this series had bronchial carcinoid tumors, only the four patients with severe diarrhea had this type of tumor. Three of the patients with severe diarrhea developed metabolic acidosis while the fourth patient had severe hypokalemia. In the three patients in which it was used, parachlorophenylalanine, an inhibitor of serotonin synthesis, improved the life-threatening diarrhea. /Former/

CP-10,188

Phenylalanine, 4-chloro-: INACTIVE