Uses
antiemetic, antipsychotic
Definition
ChEBI: A substituted phenothiazine in which the ring nitrogen at position 10 is attached to C-3 of an N,N-dimethylpropanamine moiety.
Hazard
Toxic by ingestion.
Description
This phenothiazine with sedative properties is used in
human medicines and has induced contact dermatitis
in nurses or in those working in the pharmaceutical
industry. It is also used in veterinary medicine to avoid
mortality of pigs during transportation. It is a sensitizer
and a photosensitizer.
Chemical Properties
Oily liquid; amine odor.
Brand name
Thorazine (GlaxoSmithKline).
Synthesis
Chlorpromazine, 2-chloro-10-(3-dimethylaminopropyl)phenothiazine, is synthesized in an analogous manner, except by alkylation of 2-chlorophenothiazine with 3-dimethylaminopropylchloride.
Environmental Fate
Acute and chronic toxicity due to chlorpromazine generally
manifests as an extension of normal pharmacological activity.
The precise mechanism of action of chlorpromazine, and other
phenothiazines, is unknown; however, it is thought to primarily
involve antagonism of dopaminergic (D2) neurotransmission
at synaptic sites and blockade of postsynaptic dopamine
receptor sites at the subcortical levels of the reticular formation,
limbic system, and hypothalamus. This activity contributes to
chlorpromazine’s extrapyramidal reactions. Chlorpromazine
also has strong central and peripheral activity directed against
adrenergic receptors and weak activity against serotonergic,
histaminic (H1), and muscarinic receptors. Chlorpromazine
has slight ganglionic blocking action. Chlorpromazine is
known to depress vasomotor reflexes medicated by the hypothalamus
and/or brain stem; inhibit release of growth hormone;
antagonize secretion of prolactin release-inhibiting hormone;
and reduce secretion of corticotropin-regulatory hormone.
Chlorpromazine also has direct effects on cardiac myocytes;
it can induce early after-depolarizations, block depolarizing
sodium channels, and cause significant prolongation of the
QTc interval.
Chlorpromazine may be irritating to eyes, mucous
membranes, and skin. Contact and inhalation should be
avoided.
Metabolic pathway
The in vivo photodegradation of chlorpromazine in rat
skin exposed to UV-A results in the formation of
promazine and 2-hydroxypromazine in irradiated rats,
but not in the skin of rats kept in the dark.
Chlorpromazine sulfoxide is a major metabolite of
chlorpromazine, found in smaller quantity in the skin of
irradiated rats compared with those kept in the dark.
Chlorpromazine sulfoxide is not a photoproduct of
chlorpromazine under the experimental conditions.
Toxicity evaluation
Chlorpromazine exists as both a vapor and particulate at
ambient atmospheric conditions. Chlorpromazine vapor is
degraded by photochemically produced hydroxyl radicals
with an estimated half-life of 1.6 h. Chlorpromazine particulate
is removed by wet or dry deposition. Chlorpromazine is
likely to be immobile in soil (Koc 9900, pKa 9.3) and to
adsorb to sediment if released into water. It is not expected to
volatilize from soil or water. There is high potential for
bioconcentration.
