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phenothiazine

In the central nervous system, phenothiazines act principally at the subcortical levels of the reticular formation, limbic system, & hypothalamus. Phenothiazines generally do not produce substantial cortical depression. Phenothiazines also act at the basal ganglia, exhibiting extrapyramidal effects. Phenothiazines inhibit dopaminergic neurotransmission, through post-synaptic dopaminergic receptor antagonism & inhibition of dopamine release. Phenothiazines also inhibit alpha adrenergic, H1 histaminergic, serotoninergic, & muscarinic receptors, & may have effects on GABA, substance P, & endorphin receptors. Phenothiazines exert anti-emetic activity by inhibition of dopaminergic neurotransmission in the medullary chemoreceptor trigger zone (CTZ) of the area postrema. Through their inhibition of dopaminergic neurotransmission, phenothiazines may produce extrapyramidal reactions, dystonia, catalepsy & neuroleptic syndrome. Phenothiazines produce varying degrees of sedation without hypnosis or anesthesia. Tolerance to sedative effects develops over days to weeks. Phenothiazines increase sleep time, tend to normalize sleep patterns in psychotic patients & decrease REM sleep. Phenothiazines may cause EEG changes, including a slowing of the EEG pattern, an increase in theta & delta activity, & some decrease in fast wave & alpha activity. Phenothiazines may also lower seizure threshold & induce discharge patterns associated withseizure disorders. Phenothiazines have a poikilothermic effect via interference with hypothalamic thermoregulatory control. The chemical group at the 10 position of the phenothiazine nucleus appears to determine antipsychotic efficacy. Substitution at the 2-position generally alters the potency & incidence &/or severity of adverse reactions with relative order of potency: -CF3 > -Cl > -H = -OCH3 = CONHNH2. Phenothiazine itself has been used as a urinary tract antiseptic & an antihelmintic; however, the toxicity of the drug in producing anemia, hepatitis & skin rash precludes its use in humans. Pheno- thiazine is still used as an antihelmintic agent in veterinary medicine & as an insecticide. Laboratory: - phenothiazines in specimen - phenothiazines in gastric fluid

Interactions

drug interactions

Related

vanishing bile duct syndrome (idiopathic ductopenia)

Specific

acetophenazine (Tindal, Phentoxate, Tindala) chlorpromazine (Thorazine, Ormazine, Propaphenin, Sonazine, Chloractil) fluphenazine (Prolixin, Anatensol, Triflumethazine, Calmansial, Modecate) mesoridazine (Serentil, Calodal) methotrimeprazine; levomepromazine (Nozinan, Levoprome) methylene blue; methylthioninium chloride (Provablue, MTC) perazine; pernazine; Taxilan; Psytomin perphenazine (Trilafon) prochlorperazine (Compazine, Stemetil, Novamin, Buccastem) promazine (Sparine) promethazine (Phenergan, Farganesse) thioridazine (Mellaril, Millazine, Melleretten) trifluoperazine (Stelazine, Suprazine) triflupromazine (Vesprin, Flumazin) trimeprazine; alimemazine (Nedeltran, Panectyl, Repeltin, Therafene, Theraligene, Theralen, Theralene, Vallergan, Vanectyl, Temaril)

General

heterocyclic compound, 3 rings

Database Correlations

PUBCHEM cid=7108

References

  1. Merck Index, IIth ed, Merck & Co, Rahway NJ, 1989 # 7220
  2. AHFS 96 Drug Information, GK McEnvoy et al (ed), American Society of Health-System Pharmacists, Bethesda, MD 1996
  3. Medical Knowledge Self Assessment Program (MKSAP) 11, American College of Physicians, Philadelphia 1998