Review Article
The First Generation and Second Generation Antipsychotic Drugs and their Pharmacology in Treatment of Schizophrenia
Afroj A Shaikh*, Jaydeep B Pawar and Sachin J Anbhule
Corresponding Author: Afroj A Shaikh, Department of Pharmacology, HSBPVT, GOI, Faculty of Pharmacy, Kashti, Shrigonda 413701, India.
Received: October 13, 2022; Revised: October 22, 2022; Accepted: November 11, 2022 Available Online: November 22, 2022
Citation: Shaikh AA, Pawar JB & Anbhule SJ. (2023) The First Generation and Second Generation Antipsychotic Drugs and their Pharmacology in Treatment of Schizophrenia. J Pharm Drug Res, 6(1): 661-667.
Copyrights: ©2023 Shaikh AA, Pawar JB & Anbhule SJ. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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In this review report, an attempt made to present an overview of schizophrenia & those drugs which are used in treatment of psychiatric disorders as well as some treatments for psychosis. In 1908, the schizophrenia word was coined by Eugen Bleuler (Swiss psychiatrist). The use antipsychotics as medication began from 1933 in France. Laborit and Huguenard administrated the aliphatic Phenothiazine, Chlorpromazine during surgery due to its potential anesthetic effect, in 1951. Thereafter, Hamon and Delay extended the use of this treatment in psychiatric patients. Due to abnormal brain structure & functioning occurs schizophrenia as well as psychotic disorders. Schizophrenia is a condition in people unable to differentiate between real & imaginary world. In this article we all know about Schizophrenia & Antipsychotics drugs. In that include symptoms & their types, cause, risk factor, antipsychotics classification & their pharmacology etc. In that there are three types of symptoms namely positive, Negative, Cognitive. Exact causes of schizophrenia are unknown. In the treatment of Schizophrenia or psychotics disorders the physicians commonly used antipsychotic medicines or drugs to treat their symptoms. Antipsychotic drugs further divided into two major classes namely Typical & Atypical antipsychotics. Chlorpromazine is the first medicine or drug which is used to treat symptoms of schizophrenia and schizoaffective disorders. Clozapine is most effective or potent antipsychotics drug. Which is belongs to the atypical antipsychotics which are reducing the risk of schizoaffective patients. Physicians recommend a combination of antipsychotics along with psychotherapy. In this article we have covered Brahmyadiyoga is an Ayurvedic remedies.

Keywords: Psychosis, Mental disorder, Schizophrenia, Antipsychotics, Brahmyadiyoga, Ayurvedic treatments

Schizophrenia is complex, long-term mental illness illustrated by many symptoms such as delusion, hallucination, speech disorders etc. [1]. “The word “Schizophrenia” comes from Greek word “Schizo” means “Split” & “Phrene” means “Mind”. In 1908, the term Schizophrenia was introduced by the Sweden psychiatrist Eugen Bleuler [2]. According to WHO [3], almost 20 million peoples worldwide suffer from a disease called schizophrenia & WHO has declared schizophrenia to be one of the ten leading causes of developed countries in the world [4]. Antipsychotic means those drugs or medicines used to treat psychiatric disorders like schizophrenia, bipolar disorder, schizoaffective conditions etc. In 1950, some new classes of medications come under the psychiatric practice such as antipsychotics. French pharmaceutical company Rhone-Poulenc synthesized chlorpromazine in 1950s, but not used in treatment of schizophrenia & In the US in 1960, the first clinical trial of chlorpromazine conducted with other antipsychotics. The two psychiatrics namely Jean Delay & Pierre Deniker used chlorpromazine on the patients who suffering from psychiatric disorder such as mania & schizophrenia [5].

Schizophrenia is psychiatric disorders that are affect the thinking, behaves, emotions etc. of the patients. The symptoms of schizophrenia are commonly observed at the age of 16-30. The symptoms of schizophrenia are divided into three types: Positive, Negative & Cognitive symptoms [6]. Antipsychotics medications are principally used in treatment of schizophrenia & other psychotic disorders such as mental sickness, bipolar disorder, etc. Antipsychotic medications are classified into two major classes Typical & 
Atypical it’s also called first- & second-generation drugs [7]. Antipsychotic drugs are taking around 7-14 days to reach their desire therapeutic effect. Antipsychotics unable to treat negative symptoms & able to treat / cure positive symptoms of schizophrenia. Atypical antipsychotics shows/ possess negative symptoms such as incapable to feel pleasure (Anhedonia), Alogia, Flattening, Apathy, Avolition etc. [2].


The psychological symptoms of schizophrenia are divided into three main classes: Positive, Negative & Cognitive Symptoms. While Positive & Cognitive Symptoms are almost omnipresent in schizophrenia, Positive symptoms have unrelated with cognitive symptoms. However, this relationship appeared to be accompanied by negative symptoms [8].

  1. Positive Symptoms:

Positive symptoms are related with the hyperdopaminergic transmission occurring in the mesolimbic region of brain. Dopamine Receptor Antagonist drugs such as Chlorpromazine & Haloperidol are used to reduce the positive symptoms of schizophrenia [9]. It is associated with psychological behavior that is not widespread in an enthusiastic person. Suffering people may lose a touch of truth. Following some symptoms include such as delusions, hallucination, dysfunctional way of intellectual, agitated body movement, thought disorder & lack of speaking etc. [6,9].

  1. Negative Symptoms:

A negative symptom indicates the abnormal normal mental function involving thoughts, behaviors & perceptions [10]. From these interruptions they can vary in general feelings and behaviors. The flat effect that the expression of emotions is reduced by facial expressions or tone of voice. Difficultly in initiating and sustaining activity and mutism (Speak Disorder) [9]. In Negative Symptoms you might notice: Anhedonia, Alogia, Flattening, Apathy, Avolition etc. [10].

  1. Cognitive Symptoms:

The cognitive symptoms of schizophrenia are belongs to thinking of persons. Although cognitive symptoms aren’t used to detect schizophrenia [11]. These symptoms can vary from person to person [12]. Victims may experience normal to serious changes in their intelligence or in any other aspect of thought. Symptoms may include difficulty concentrating; memory problem, lack of execution facilities, i.e. difficulty in understanding information & making decisions [5]. In it seen some symptoms such as unable to concentrate, memory problems, reduced executive function, lack of insight etc. [11].


An exact cause of Schizophrenia is unknown. Researchers are continuously trying to find about the etiology of the disease [13] but abnormal brain structure, enter-changes in neurotransmitter functioning, genetic & environmental factors cause schizophrenia [11].

Risk Factor (Figure 1)


Antipsychotic is a drug which are used to treat symptoms of psychosis. They are also used to treat Schizophrenia, Depression, Bipolar disorder, Schizo affective disorders & Anxiety. Antipsychotics drugs shows adverse effect [15].

Classification of Antipsychotic Drugs

Antipsychotic drugs are classified into two subtypes such as Typical (First generation) & Atypical (Second generation). Typical medications have been used since the 1950s. It’s oldest or first type of antipsychotic drugs or medicines. Atypical medications have been used since the 1990s. It’s new or second type of antipsychotic class of drugs [16]. The use of antipsychotic drugs has the benefit of reducing the symptoms of psychosis and the risk of numerous side effects, including a difficult trade-off. Antipsychotic drugs are not therapeutic & do not eliminates long term thought disorders but they often negate the power of illusion, delusions & allow a person with schizophrenia to act in a caring situation (Figure 2) [13].

Antipsychotic medicine is a principle psychological strategy for the treatment of schizophrenia. These substances limit the effectiveness of treatment in individual patients & are associated with side effects. Taking antipsychotics is considered. While these drugs have no effect on negative symptoms. All of these drugs stop the action of postsynaptic dopamine D2 receptors. However, modern medicine has a wide spectrum of targeted Serotonin, nor epinephrine, Acetylcholine, Histamine & Glutamate. Clozapine, considered an atypical antipsychotic, is associated with a variety of neuroreceptors (Dopamine, 5-HT serotonin & noradrenergic receptor) & and some acts as a multi-neuroreceptor antagonist. Clozapine is the most potent or highly effective antipsychotic drug & it’s does also reduce the risk of suicide of schizoaffective patients who tolerate to other antipsychotic drugs [2].

Mechanism of Action

There are many drugs used to treat schizophrenia & they have different mechanism of action to create desired therapeutic effects. Mostly antipsychotics drugs help to treat Schizophrenia [17].

1st Generation

The first generation of antipsychotics follows inhibiting mechanism. They are highly effective when they block 72% of the D2 dopamine receptors in the brain. They also show antagonism action at the Noradrenergic, Cholinergic & Histaminergic receptors. It’s mainly used to treat positive symptoms such as hallucinations & delusions [7,18]. In Typical antipsychotics show some adverse effect such extra-pyramidal side effects & anticholinergic adverse effect such as dry mouth, constipation etc. sedation, abnormal heart rates, sudden death, seizure threshold, hypotension, discoloration of skin, hydration, confusion, fever, acute renal failure etc. as well it’s have some contraindications like CNS depressant, cardiac abnormalities, history of allergy & seizure disorders, prostatic hypertrophy, dyskinesia, etc. [7].

2nd Generation

The second generation of antipsychotics follows blocking mechanism. Its block the D2 dopamine receptors as well as serotonin receptors antagonist. 5-HT2A sub-type of the serotonin receptor is most commonly involved, thus may be associated with reduced risk of these adverse effect. In 2016, 12 Atypical Antipsychotics are approved by Food & Drug Administration (FDA) [7,18]. In Atypical antipsychotics show some side effects such as weight gain, metabolic syndrome development, dizziness, anxiety, sedation, thermo-sensitive, increased appetite, somnolence, hypotension, agitation, headache, restlessness, hyper salivation, etc. and it have some contraindications like parkinsonism, narcoleptic, tardive dyskinesia, during pregnancy, glaucoma, liver disease, severe neutropenia, deficiency hexosaminidase etc. [7].


Antipsychotic Drugs

Physician recommended a combination of psychotic drugs along with the psychotherapy (Tables 1 & 2).

Ayurvedic Treatment

Brahmyadiyoga is an herbal preparation which is used in the treatment of Schizophrenia. Brahmyadiyoga developed by Central Council for Ayurveda & Siddha, under Ministry of Health & Family Welfare of India. It includes Brahmi, Jatamansi, Sarpagandha, Vacha, Kusta, Tagar etc. For the treatment of schizophrenia, herbal combination of water-based extract of bramhi & Jatamansi are as effective as modern antipsychotics drugs (Table 3) [6].


We concluded from this review article; schizophrenia is a complex psychiatric disorder that is belong to the disordering of brain improvement caused by environmental as well as some genetic factors. Most schizophrenia as well as psychotic disorders occurs due to abnormal brain structure & functioning. In this article we discuss about pharmacology of antipsychotics & Ayurvedic Treatment of psychosis. In that we observe delusion, hallucination, speech & behavior disorder like symptoms. In this we know about pharmacology of antipsychotics drugs but their exact causes of schizophrenia are unknown, I hope in future our researches are find exact causes of schizophrenia.


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