Biomaterial Database

Phenothiazine drug metabolites: dopamine D2 receptor, alpha 1- and alpha 2-adrenoceptor binding. 1986

P A Hals, and H Hall, and S G Dahl

The in vitro binding affinities of levomepromazine, chlorpromazine, fluphenazine, perphenazine and methoxypromazine and their main metabolites to dopamine D2 receptors, alpha 1- and alpha 2-adrenoceptors in rat brain, were examined using [3H]spiperone, [3H]WB 4101 and [3H]yohimbine binding. All compounds had 10-500 times lower affinities to alpha 2-adrenoceptors than to dopamine D2 receptors and alpha 1-adrenoceptors. Ring-hydroxylated and N-demethylated metabolites had relative potencies for dopamine D2 receptor and alpha 1-adrenoceptor binding ranging from 20 to 70%, compared to that of the parent drugs. The ring sulphoxides of levomepromazine, chlorpromazine and perphenazine, except dextro levomepromazine sulphoxide, were virtually inactive in all binding systems. The results indicate that the metabolites having the highest binding affinities for dopamine D2 receptor and alpha 1-adrenoceptor binding may contribute significantly to the therapeutic effect and side-effects of the drugs, and should be measured together with the parent drugs in blood level-effect studies.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D008297	Male		Males
D008728	Methotrimeprazine	A phenothiazine with pharmacological activity similar to that of both CHLORPROMAZINE and PROMETHAZINE. It has the histamine-antagonist properties of the antihistamines together with CENTRAL NERVOUS SYSTEM effects resembling those of chlorpromazine. (From Martindale, The Extra Pharmacopoeia, 30th ed, p604)	Levomeprazin,Levomepromazine,Levopromazine,Tisercin,Tizercine,Tizertsin
D011919	Rats, Inbred Strains	Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.	August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D011942	Receptors, Adrenergic, alpha	One of the two major pharmacological subdivisions of adrenergic receptors that were originally defined by the relative potencies of various adrenergic compounds. The alpha receptors were initially described as excitatory receptors that post-junctionally stimulate SMOOTH MUSCLE contraction. However, further analysis has revealed a more complex picture involving several alpha receptor subtypes and their involvement in feedback regulation.	Adrenergic alpha-Receptor,Adrenergic alpha-Receptors,Receptors, alpha-Adrenergic,alpha-Adrenergic Receptor,alpha-Adrenergic Receptors,Receptor, Adrenergic, alpha,Adrenergic alpha Receptor,Adrenergic alpha Receptors,Receptor, alpha-Adrenergic,Receptors, alpha Adrenergic,alpha Adrenergic Receptor,alpha Adrenergic Receptors,alpha-Receptor, Adrenergic,alpha-Receptors, Adrenergic
D011954	Receptors, Dopamine	Cell-surface proteins that bind dopamine with high affinity and trigger intracellular changes influencing the behavior of cells.	Dopamine Receptors,Dopamine Receptor,Receptor, Dopamine
D001921	Brain	The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.	Encephalon
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001711	Biotransformation	The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alterations may be divided into METABOLIC DETOXICATION, PHASE I and METABOLIC DETOXICATION, PHASE II.
D014150	Antipsychotic Agents	Agents that control agitated psychotic behavior, alleviate acute psychotic states, reduce psychotic symptoms, and exert a quieting effect. They are used in SCHIZOPHRENIA; senile dementia; transient psychosis following surgery; or MYOCARDIAL INFARCTION; etc. These drugs are often referred to as neuroleptics alluding to the tendency to produce neurological side effects, but not all antipsychotics are likely to produce such effects. Many of these drugs may also be effective against nausea, emesis, and pruritus.	Antipsychotic,Antipsychotic Agent,Antipsychotic Drug,Antipsychotic Medication,Major Tranquilizer,Neuroleptic,Neuroleptic Agent,Neuroleptic Drug,Neuroleptics,Tranquilizing Agents, Major,Antipsychotic Drugs,Antipsychotic Effect,Antipsychotic Effects,Antipsychotics,Major Tranquilizers,Neuroleptic Agents,Neuroleptic Drugs,Tranquillizing Agents, Major,Agent, Antipsychotic,Agent, Neuroleptic,Drug, Antipsychotic,Drug, Neuroleptic,Effect, Antipsychotic,Major Tranquilizing Agents,Major Tranquillizing Agents,Medication, Antipsychotic,Tranquilizer, Major