ATC Group: N05A Antipsychotics

Amisulpride is a neuroleptic. Amisulpride binds selectively with a high affinity to human dopaminergic D₂/D₃ receptor subtypes whereas it is devoid of affinity for D₁, D₄ and D₅ receptor subtypes.

It has been proposed that aripiprazole’s efficacy in schizophrenia and Bipolar I Disorder is mediated through a combination of partial agonism at dopamine D₂ and serotonin 5-HT_1A receptors and antagonism of serotonin 5-HT_2A receptors.

The mechanism of action of asenapine is not fully understood. However, based on its receptor pharmacology, it is proposed that the efficacy of asenapine is mediated through a combination of antagonist activity at D₂ and 5-HT_2A receptors. Actions at other receptors e.g. 5-HT_1A, 5-HT_1B, 5-HT_2C, 5-HT₆, 5-HT₇, D₃, and a₂-adrenergic receptors, may also contribute to the clinical effects of asenapine.

Benperidol is a strong dopamine receptor antagonist with weaker serotonin receptor antagonism. In high doses, it has antihistaminergic and alpha-adrenergic properties. It possesses minimal anticholinergic properties. Benperidol is a typical antipsychotic primarily used to treat hypersexuality syndromes and can be used to treat schizophrenia.

Brexpiprazole is an atypical antipsychotic agent. The pharmacology of brexpiprazole is believed to be mediated by a modulatory activity at the serotonin and dopamine systems that combines partial agonist activity at serotonergic 5-HT_1A and at dopaminergic D₂ receptors with antagonist activity at serotonergic 5-HT_2A receptors, with similar high affinities at all of these receptors.

Cariprazine is indicated for the treatment of schizophrenia in adult patients. The mechanism of action of cariprazine is not fully known. However the therapeutic effect of cariprazine may be mediated through a combination of partial agonist activity at dopamine D₃, D₂ (Ki values of 0.085-0.3 nM versus 0.49-0.71 nM respectively) and serotonin 5-HT_1A receptors (Ki values of 1.4-2.6 nM), and antagonist activity at serotonin 5-HT_2B, 5-HT_2A and histamine H₁ receptors (Ki values of 0.58-1.1 nM, 18.8 nM and 23.3 nM, respectively).

Chlorpromazine is a phenothiazine neuroleptic. Chlorpromazine has depressant actions on the Central Nervous System, with alpha-adrenergic blocking and anticholinergic activities. It has anti-emetic, anti-puritic, serotonin-blocking and weak anti-histamine properties and slight ganglion blocking activity.

Clozapine has been shown to be an antipsychotic agent that is different from classic antipsychotics. Clozapine has potent anti-alpha-adrenergic, anticholinergic, antihistaminic, and arousal-reaction-inhibiting effects. It has also been shown to possess antiserotoninergic properties.

Droperidol is a butyrophenone neuroleptic. Its pharmacologic profile is characterised mainly by dopamine-blocking and weak α1-adrenolytic effects. Droperidol is devoid of anticholinergic and antihistaminic activity.

Fluphenazine is an ester of the potent neuroleptic fluphenazine, a phenothiazine derivative of the piperazine type. The ester is slowly absorbed from the intramuscular site of injection and is then hydrolysed in the plasma to the active therapeutic agent, fluphenazine. It is used for the treatment and maintenance of schizophrenic patients and those with paranoid psychoses.

Haloperidol is an antipsychotic belonging to the butyrophenones group. It is a potent central dopamine type 2 receptor antagonist, and at recommended doses, has low alpha-1 antiadrenergic activity and no antihistaminergic or anticholinergic activity.

The mechanism of action of iloperidone in schizophrenia and bipolar I disorder is unknown. However, the efficacy of iloperidone could be mediated through a combination of dopamine type 2 (D₂) and serotonin type 2 (5-HT₂) antagonism. Iloperidone forms an active metabolite, P88, that has an in vitro receptor binding profile similar to the parent drug.

Levomepromazine resembles chlorpromazine and promethazine in the pattern of its pharmacology. It possesses anti-emetic, antihistamine and anti-adrenaline activity and exhibits a strong sedative effect.

Levosulpiride is a selective antagonist at dopamine (D) receptors. Levosulpiride exerts a regulation action both on the central and peripheral nervous circuits controlling the dynamics of digestive system.

Little is known about the way the lithium ion can modify neurotransmission within the CNS. Many of the proposed mechanisms have suggested an inhibitory effect on components of various neurotransmitter signalling pathways, such as cyclic AMP formation, cyclic GMP formation, G-proteins or inositol phosphate metabolism.

Loxapine binds with noradrenergic, histaminergic, and cholinergic receptors, and its interaction with these systems may influence the spectrum of its pharmacological effects. Loxapine is indicated for the rapid control of mild-to-moderate agitation in adult patients with schizophrenia or bipolar disorder.

Lurasidone is a selective blocking agent of dopamine and monoamine effects indicated for the treatment of schizophrenia. Lurasidone binds strongly to dopaminergic D₂- and to serotonergic 5-HT_2A and 5-HT₇ receptors. Lurasidone does not bind to histaminergic or muscarinic receptors.

Olanzapine is an antipsychotic, antimanic and mood stabilising agent that demonstrates a broad pharmacologic profile across a number of receptor systems.

Paliperidone is a selective blocking agent of monoamine effects, whose pharmacological properties are different from that of traditional neuroleptics. Even though paliperidone is a strong D₂-antagonist, which is believed to relieve the positive symptoms of schizophrenia, it causes less catalepsy and decreases motor functions to a lesser extent than traditional neuroleptics.

Pericyazine is a neuroleptic with cardiovascular and antihistamine effects similar to those of chlorpromazine, but it has a stronger antiserotonin effect and a powerful central sedative effect.

Perphenazine is a depressant which blocks dopamine receptors in the central nervous system. It binds to dopamine D₁ and D₂ receptors and inhibits their activity. Its antiemetic action is mainly due to the inhibition of D₂ receptors in the center of the vomiting. Perphenazine also binds to alpha adrenergic receptors and in conjunction with G proteins activate the phosphatidylinositol-calcium system.

Pimavanserin is an atypical antipsychotic indicated for the treatment of hallucinations and delusions associated with Parkinson’s disease psychosis. The mechanism of action of is unclear. However, the effect of pimavanserin could be mediated through a combination of inverse agonist and antagonist activity at serotonin 5-HT_2A receptors and to a lesser extent at serotonin 5-HT_2C receptors.

Pimozide is an orally active neuroleptic drug which blocks central dopaminergic receptors. Pimozide antagonises many of the actions of amphetamine and apomorphine.

Prochlorperazine belongs to the phenothiazine group. Prochlorperazine has a wide range of activity arising from its depressant actions on the CNS and its alpha-adrenergic blocking and weaker anti-muscarinic properties. It inhibits dopamine and prolactin-release-inhibitory factor, thus stimulating the release of prolactin.

Promazine has a wide range of activity arising from its depressant actions on the central nervous system and its alpha-adrenergic blocking and weaker anticholinergic activities. Promazine is a dopamine inhibitor.

Quetiapine is an atypical antipsychotic agent. Quetiapine and the active human plasma metabolite, norquetiapine interact with a broad range of neurotransmitter receptors.

Risperidone is a selective monoaminergic antagonist with unique properties. Although risperidone is a potent D₂ antagonist, which is considered to improve the positive symptoms of schizophrenia, it causes less depression of motor activity and induction of catalepsy than classical antipsychotics.

Sulpiride is a member of the group of substituted benzamides, which are structurally distinct from the phenothiazines, butyrophenones and thioxanthenes. One of the characteristics of sulpiride is its bimodal activity, as it has both antidepressant and neuroleptic properties. Schizophrenia characterised by a lack of social contact can benefit strikingly.

Tiapride is an atypical neuroleptic which exhibits selectivity in in-vitro studies for D₂ and D₃ dopamine subtype receptors without any affinity for subtype receptors of the principal central neurotransmitters (including serotonin, noradrenaline and histamine).

Trifluoperazine is one of the phenothiazine class of compounds and as such has many pharmacodynamic effects which relate to its therapeutic actions and side effects. The most notable action of phenothiazines is antagonism at dopamine receptors in the CNS.

Ziprasidone has been shown to be an antagonist at both serotonin type 2A (5HT_2A) and dopamine type 2 (D₂) receptors. It is proposed that the therapeutic activity is mediated, in part, through this combination of antagonist activities. Ziprasidone is also a potent antagonist at 5HT_2C and 5HT_1D receptors, a potent agonist at the 5HT_1A receptor and inhibits neuronal reuptake of norepinephrine and serotonin.

Zuclopenthixol is a potent neuroleptic of the thioxanthene series with a piperazine side-chain. The antipsychotic effect of neuroleptics is related to their dopamine receptor blocking effect.