Dopamine Hypothesis : This idea was suggested by observation that drugs which reduced dopaminergic activity reduced acute symptoms/signs of psychoses. Symptoms notably Decreased -- agitation anxiety hallucinations
Four pathway of dopaminergic neurotransmission 1)Mesolimbic-mesocortical pathway (one most closely related to behavior ) 2)nigrostriatal pathway(it is involved in the coordination of voluntary movement) 3)tuberoinfundibular pathway (inhibits prolactin secreation) prolactin 4 ） medullary-periventricular pathway (the function is not clear,may be involved eating behavior)
Dopamin receptor: two type, five subtype - DA1 (D1-like receptor): D1,D5 - DA2 (D2-like receptor): D2,D3, D4
Pharmalogical effects Antiemetic effect. - This is a results of blocking DA2 receptor. -In low doses, blocking DA2 receptor in chemoreceptor trigger zone(CTZ). -In high doses, chlorpromazine may directly depress the medulla vomiting center.
Pharmalogical effects Altering temperature-regulating mechanisms. in a cold climate it decrease temperature in body in a hot climate they can cause hyperthermia
Pharmalogical effects Endocrine system effect Increasing the lactogenic hormone( 催乳 素 ).Increased levels of prolactin may lead to galactorrhea （溢乳 ). phenothiazines decrease FSH and ACTH. Decreasing release and secretion of pituitary growth hormone.
Therapeutic uses 1. Psychotic disorders, all kind of schizophrenia. 2. Nausea and vomiting.(except carsickness). 3. Decrease the temperature. 4. Control of intractable hiccup （呃逆打 嗝 ). 5.Therapy gigantism( 巨人症 ).
untoward effects (1) Special side effect: Extrapyramidal symptoms A. Parkinsonian syndrome: the patients display rigidity( 僵化 )and tremor B. Acut dystonia: patients display facial grimacing ( 面部的歪扭,) torticollis( 斜颈 ) C.Akathisia ( 静坐不能 ) D. tardive dyskinesia ( 迟发性运动障碍）tardive dyskinesia
patient display sucking of the lips and other involuntary facial movement. (The dyskinesia may persist for after discontinuation of the therapy).
Untoward effects (2)General side effect: A. CNS depression B. M-receptor blocking: The symptom of M- receptor blocking C. Orthostatic hypotension
Untoward effects (3)Inducing psychosis by drug (4)seizure and epilepsy (5)allergic reaction (6)cardiovascular effect
Untoward effects (7)Endocrine disorder: Hyperprolactinemia--causes: For women: Amenorrhea(abnormal suppression or absence of menstrual flow), galactorrhea, infertility For men: impotence infertility,diminished libido For children: decreasing growth.
Drug interaction: 1)Increasing CNS inhibition with ethanol, sedative-hypnotics, morphine. 2)Inhibiting the of L-Dopa (agonist of the doparmin-receptor). 3)Increase the dose with phentoin and carbamazepine.
Atypical antipsychotic drugs Clozapine and Risperidone selectively inhibit D4 and 5-HT 2 -receptors. Risperidone selectively inhibit D2 and 5-HT 2 - receptors. Sulpiride selectively inhibit D2-receptors in the mesolimbic and mesocortical areas of the brain. Sulpiride,Clozapine and risperidone have low risk of extra-pyramidal adverse reaction.
Atypical antipsychotic drugs Sulpiride Selectively inhibit D2-receptors in the mesolimbic and mesocortical areas of the brain. Producing low extra-pyramidal adverse reaction.
Pharmacodynamics Possible mechanisms of action: -effects on electrolyte/ion transport neurotransmitter -neurotransmitter release modulation influence on second messengers. Lithium salts how to affect second messengers?(learning by yourself)
Overview Depression is an alteration of mood characterized by sadness, worry, and anxiety. The patient may suffer from losses of weight, libido, and enthusiasm.
Depression Clinical depression is a syndrome that may include: Sustained mood disturbances Impaired memory and concentration Disturbed sleep Reduced energy level Reduced libido Impaired sleep.
Depression Patient complaints suggestive of depression may include: Pain (headaches, body aches) A mood of apathy, anxiety, or irritability Sexual complaints low energy, excessive tiredness reduced capacity for enjoyment.
Classification of Antidepressant Drugs Five of antidepressant Tricyclic antidepressants (TCA) Monoamine oxidase inhibitors (MAO) NA reuptake inhibitors Serotonin-specific reuptake inhibitors (SSRIs) Serotonin and NA-specific reuptake inhibitors
Most antidepressants are believed to improve by increasing NT Catecholamine 5-HT stores
Pharmalogic effects CNS -In the depressed patients, an elevation of mood occur 2-3 weeks after administration begins, the latency period can be as long as 4 weeks. -The imipramine blocks the re-uptake of serotonin and NA
Pharmalogic effects Autonomic nervous system Blocking m-receptor
Home work Suggested further readings Rojas-Corrales,MO.and Mico JA. Antipressant-like effects of tramadol and other central analgesics with activity on monoamines reuptake, inhelpless rats.life science.2002,72(2):143- 152
1.How are agents in this chapter classified? 2.Describe the pharmacological effects of Chlorpromazine. What are the major differences between the TCA and SSRIs?