Haloperidol Injection - Pharmaceutical Information, Clinical Trials, Detailed Pharmacology, Toxicology
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Haloperidol Injection - Scientific Information

Manufacture: Fresenius Kabi USA, LLC
Country: Canada
Condition: Agitation, Mania, Schizophrenia
Class: Antipsychotics
Form: Liquid solution, Intramuscular (IM)
Ingredients: Haloperidol

Pharmaceutical Information

Drug Substance

Proper Name: haloperidol
Chemical Name: 1-butanone, 4-[4-(4-chlorophenyl)-4-hydroxy-1-piperidinyl]-1(4-fluorophenyl)
Structural Formula:
Molecular Formula: C21H23ClFNO2
Molecular Weight: 375.87
Description: White or almost white amorphous or crystalline powder. Practically insoluble in water, very slightly soluble in ethanol, slightly soluble in ether, methylene chloride and methanol, soluble in chloroform.

Pharmacology

Haloperidol exerts pharmacological effects, characteristic of neuroleptic agents; it reduces locomotor and exploratory behaviour (ambulation and “emotional” defecation) in laboratory animals and at higher doses induces cataleptic immobility and ptosis, it suppresses the conditioned avoidance response in the jumping box test and blocks amphetamine-induced hyperactivity, and stereotypy, it suppresses apomorphine-induced emesis in dogs, it depresses food consumption and reduces weight gain, it abolishes the righting reflex in mice and prolongs barbiturate sleeping time. Haloperidol has relatively weak adrenolytic properties and at pharmacologically active doses it produces slight hypotension in the cat and hypothermia in the rat. In dogs and cats, the drug decreases the epinephrine-induced contractions of the nictitating membrane but is less effective against norepinephrine. Changes in the EEG activity produced by haloperidol are similar to those seen with phenothiazine derivatives.

Haloperidol blocks competitively postsynaptic dopamine receptors in the mesolimbic, nigrostriatal and tuberoinfundibular dopaminergic systems. Blockade of dopamine receptors in these areas is believed to bring about the antipsychotic, extrapyramidal and neuroendocrine actions of antipsychotic drugs, respectively.

Toxicology

Acute Toxicity
SPECIES LD50 (mg/kg)
IV SC ORAL
Mice 13 54 144
Rats 22 63 850
Hamsters - - 405
Rabbits 8 - -
Dogs 18 > 80 90

Long-Term Toxicity
Species Route of Administration Dose mg/kg/day Duration Results
Rat Oral 1 12 months No drug-induced abnormalities.
3
10
3.5 18 months No drug-induced abnormalities in blood, urine, laboratory parameters, gross pathology, histopathology. Body weights ↓, food consumption ↓, when compared to controls
6.5
14.5
33.0
Dog Oral 0.5 6 months No drug-induce abnormalities.
2.0
2.0 12 months No deaths, decreased weight gain; convulsions, tremors and emesis at high doses; transient breast engorgement and lactation between 3rd and 8th weeks were not dose-related; dose-related hepatocellular changes and elevated SGPT levels were reversible upon discontinuation of treatment.
6.0
12.0
Rat Intramuscular 1.0 4 weeks No abnormalities in hematology, organ weights or gross pathology. Inflammatory changes at the site of injection due to repeated injections.
4.0
Dog Intramuscular 1.0 4 weeks No abnormalities in hematology, organ weights or gross pathology. Inflammatory changes at the site of injection due to repeated injections.
4.0

Reproductive Studies
Study Species Route of Administration Dose mg/kg/day Results
Pregnancy Rat Oral 0.073 Drug administered in the diet. Mating depressed in high-dose rates. No abnormalities occurred in 939 offspring. No significant difference between litter size of control and experimental groups. Offsprings from haloperidol-treated dams slightly smaller.
0.65
1.90
Rat Intravenous 0.6 Administered from 6th to 18th day post mating. No abnormalities observed in 663 offspring. No significant difference in litter size, mortality of the offspring or average delivery time.
1.8
3.0
Dog Oral 1.0 No malformations in 94 pups. No effect on pregnancy or average litter size.
2.0
4.0
Delivery Rat Intramuscular 0.125 Drug administered just prior to delivery. No abnormalities and no effect on litter size. Up to 1 mg/kg no effect on delivery time. At 4 mg/kg, increase in delivery time and increase in mortality of the young due to failure to remove placenta from the offspring by the depressed dams.
0.25
1.0
4.0
Lactation Rat Intravenous 0.6 From 1st to 6th day after delivery. Little or no significant difference in the mortality weight and gross pathology between the offspring from untreated control dams and those to which haloperidol was administered.
1.8