Schizophrenia adrenergic receptors

As drugs of mixed action, amphetamines activate adrenergic receptors and simultaneously release endogenic catecholamines (norepinephrine and dopamine) from neurons of the brain and periphery. Sympathomimetic effects on the periphery are very similar to those of ephedrine. Amphetamine elevates systolic and diastolic blood pressure and has weakly expressed, broncholytic action. These effects are more prolonged, yet less expressed, than with epinephrine. The distinctive feature of amphetamines is their psychostimulatory activity. Larger doses can cause hallucinations and mental conditions similar to paranoid schizophrenia. As a sympathomimetic, amphetamine is sometimes used for uterine inertia. Synonyms of amphetamine are phenamine and benzedrine. 

Although pharmacological evidence suggests an important role for the adrenergic system in schizophrenia, few studies of receptor expression in postmortem brain in schizophrenia have been conducted. In the PFC, no relationship was found between polymorphisms in the regulatory region of the a 1 A-adrenergic receptor... 

Clark DA, Mancama D, Kerwin RW, Arranz MJ. 2006. Expression of the alphalA-adrenergic receptor in schizophrenia. Neurosci Lett 401 248-251. 

Bolonna AA, Arranz MJ, Munro J, Osborne S, Petouni M, et al. 2000. No influence of adrenergic receptor polymorphisms on schizophrenia and antipsychotic response. Neurosci. Lett. 280 65-68... 

Fig. 11.1 C-11 raclopride images of a patient with schizophrenia before and after treatment with Ziprasidone, which binds to dopamine, serotonin and alpha-adrenergic receptors in the basal ganglia.

Sertindole is one of the newer antipsychotic medications for the treatment of schizophrenia. It mainly affects dopamine D2, serotonin 5-HT2, and oti-adrenergic receptors. In contrast to other antipsychotics, sertindole is not associated with sedative effects sedation may add to the cognitive problems inherent in schizophrenia. 

Ziprasidone is an atypical antipsychotic in clinical use for both schizophrenia and bipolar disorder (see footnote 1). It has a high affinity for dopamine, serotonin, and alpha-adrenergic receptors and a moderate affinity for histamine receptors. The exact mechanism of action of ziprasidone is unknown. However it has been presumed that its antipsychotic activity is mediated primarily by antagonism at dopamine receptors, specifically D2. Serotonin antagonism may also play a role in the effectiveness of ziprasidone. Antagonism at histaminic and alpha adrenergic receptors are likely responsible for some of the side effects of ziprasidone, such as sedation and orthostasis. The worldwide sales of ziprasidone are expected to be 1 billion in 2009. 

PD Zeprexa is a selective monoaminergic antagonist with high affinity for the following receptors serotonin 5HT, dopamine, muscarinic, histamine, and adrenergic. Its action on schizophrenia is through the antagonism in serotonin and dopamine. 

Mecfianism of Action A piperazine derivative that antagonizes alpha-adrenergic, dopamine, histamine, and serotonin receptors also inhibits reuptake of serotonin and norepinephrine. Therapeutic Effect Diminishes symptoms of schizophrenia and depression. 

Risperdal Risperidone 0.25, 0.5, 1, 2, 3, 4 mg Tablet Schizophrenia A selective monoaminergic antagonist (5HT2, dopamine type 2 (D2), al and a2 adrenergic, and HI histaminergic receptors Colloidal silicon dioxide, hypromellose, lactose, magnesium stearate, MCC, propylene glycol, sodium lauryl sulfate, corn starch Janssen Pharmaceuticals... 

Despite the preponderance of data correlating the dopamine D2 receptor with schizophrenia, alternative sites in the brain (serotonergic, adrenergic, glutamatergic, and GABAergic) are also being investigated to explain the actions of atypical neuroleptics. 

Olanzapine Alcohol Olanzapine is a second generation antipsychotic used to treat schizophrenia and mania related to bipolar disorder. Olanzapine binds neurotransmitter receptors of several classes including dopaminergic, adrenergic, and serotonergic receptors [249, 250]. 

Ciozapine (Clozaril) Antipsychotic mechanism unclear. Blocks dopamine receptors as well as cholinergic, adrenergic, serotonergic histaminergic neurotransmission. Schizophrenia in those whom traditional antipsychotics have failed or have produced intolerable side effects. Very few extrapyramidal side effects. Potent antimuscarinic effects. Agranulocytosis in 2%. No tardive dyskinesia or increased prolactin release. 

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