Alnespirone [S 20499] is a potent and full agonist at pre- and postsynaptic serotonin 1A receptors. Alnespirone is the (+)-enantiomer, S 20244 is the racemate. In animal models, alnespirone demonstrated both anxiolytic and antidepressant activity and was undergoing phase II trials in these indications with Servier in France. However, development of Alnespirone was discontinued for anxiety disorders and major depressive disorder.

Lensiprazine (SLV314) is a potent D2 receptor antagonist in vitro and have a considerable in vitro affinity for serotonin reuptake sites. It capable of antagonizing apomorphine-induced climbing behavior, disrupting CAR activity and potentiating 5-hydroxytryptophan (5-HTP) behavior. SLV314 has also been found to antagonize amphetamine- and ketamine-stimulated locomotor activity and methylphenidate-induced gnawing and stimulated behaviors, furthermore, a significant dose discrepancy was seen between the antipsychotic and cataleptogenic effects of SLV314. Lensiprazine demonstrated putative antipsychotic and selective serotonin reuptake inhibitor potential.

Befiperide, a non-dopaminolytic serotonin 1 receptor agonist, was a neuroleptic for psychotic disorders. However, further studies for this drug were discontinued.

Brolamfetamine (also known as DOB, bromo-DMA, and 4-bromo-2,5-dimethoxyphenylisopropylamine) is one of a vast number of compounds used recreationally to achieve hallucinogenic effects. Brolamfetamine is one of the most potent hallucinogens, with its hallucinogenic potency directly linked to its abuse potential. Brolamfetamine acts as a partial agonist of 5HT2A, 5HT2B, 5HT2C, and TAAR1 receptors, but it’s psychedelic effects are mainly mediated by its agonistic properties at the 5-HT2A receptor. Animal studies have shown physiologic effects including hypertension, tachycardia, hyperpyrexia, pupillary dilatation, and peripheral vasoconstriction. In general, Brolamfetamine having a similar effect to LSD, with slower onset (up to 3–4 h to peak intoxication) and longer duration of effect (up to 36 h). Brolamfetamine is not commonly available, through periods of higher circulation were reported in Australia in 1983, Ireland in 2003, and in Italy in 2015. Brolamphetamine, as well as many other synthetic hallucinogens, are increasingly being sold as LSD. Internationally Brolamfetamine is a Schedule I drug under the Convention on Psychotropic Substances. Due to its selectivity, Brolamfetamine is often used in scientific research when studying the 5-HT2 receptor subfamily.

Eptapirone is a potent, selective and efficacious 5-HT1A receptor agonist. In rats, it is readily bioavailable after oral administration. Likely, because of its high efficacy at 5-HT1A receptors, Eptapirone exerted powerful antidepressant- and anxiolytic-like activity in animal models. Eptapirone given in the evening suppresses REM (rapid eye movement) sleep more than buspirone and implies a greater central effect on serotonin receptors, which is consistent with the preclinical data that indicate it has greater efficacy than buspirone. It has little effect on other sleep stages. Eptapirone has been in phase I clinical trials for the treatment of anxiety and major depressive disorder. However, this research has been discontinued.

Eltoprazine, a 5-HT1A/B receptor partial agonist, was created by Duphar in the 1980s (as DU-28853) and was subsequently developed by Solvay to treat pathological aggression. This drug is in clinical development for the treatment of Parkinson's disease levodopa-induced dyskinesia (PD-LID), Alzheimer's aggression and adult attention deficit hyperactivity disorder (adult ADHD). In addition, was shown, that the drug could be useful for normalizing prefrontal cognitive abilities, reducing aggression and impulsivity, and improving cognitive function in schizophrenia.

Fluprazine (previously known as DU27716), a psychoactive drug was studied as a behaviorally selective, anti-aggressive agent. Experiments on rodents have shown that fluprazine didn’t appreciably affect defensive attack or other defensive behaviors even though it strongly inhibited offensive attack. This agent is used to test both differences and similarities in neurochemical substrates and adaptive significance of different forms of intraspecific aggression.

IPSAPIRONE, an azapirone derivative structurally unrelated to the benzodiazepines, is a selective 5-HT1A serotonin receptor agonist. It has antidepressant and anxiolytic effects. IPSAPIRONE was studied in several clinical trials for depression and generalized anxiety disorder.

Quizapine is a piperazine-based nonselective serotonin (5-HT) receptor agonist with antidepressant and oxytocic activities. Quipazine targets and binds to serotonin receptors, particularly to the 5HT2A and 5HT3 receptors. Quipazine is a potential anti-parkinsonian agent. Serotonin receptor activation by quipazine may lead to smooth muscle contraction and antidepressant effects. quipazine, a central serotonergic agent, counteracted some of the drug-induced symptoms of pseudoparkinsonism in laboratory animals. Cholinergic, dopaminergic and histaminergic receptors play an important role in the manifestations of these symptoms.

Lysergide (LSD) is a semi-synthetic hallucinogen and is one of the most potent drugs known. Recreational use became popular between the 1960s to 1980s, but is now less common. During the 1960s, LSD was investigated for a variety of psychiatric indications, including the following: as an aid in the treatment of schizophrenia; as a means of creating a "model psychosis"; as a direct antidepressant; and as an adjunct to psychotherapy. LSD is listed in Schedule I of the United Nations 1971 Convention on Psychotropic Substances. LSD possesses a complex pharmacological profile that includes direct activation of serotonin, dopamine and norepinephrine receptors. In addition, one of its chief sites of action is that of compound-specific (“allosteric”) alterations in secondary messengers associated with 5HT2A and 5HT2C receptor activation and changes in gene expression. The hallucinogenic effects of LSD are likely due to agonism at 5HT2A and 5HT2C receptors. LSD is also an agonist at the majority of known serotonin receptors, including 5HT1A, 5HT1B, 5HT1D, 5HT5A, 5HT6 and 5HT7 receptors. L-Lysergide (L-LSD) is a non-psychoactive enantiomer of LSD. D-LSD not only completely eradicated the response to 10 muM dopamine in rat hippocampus preparations but also consistently stimulated adenylate cyclase activity. L-LSD (80 muM) was without effect. Also both D- and L-LSD bind to solubilized 5-HT1 sites with comparable high affinities, whereas D-LSD has a markedly higher affinity for the membrane 5-HT1 site. In crude bovine frontal cortical membranes, D-LSD has high affinity for the 5-HT 1 binding site (IC50 = 40 nM), while L-LSD has the very low affinity (IC50 = 10,000 nM versus [3H]5-HT). Solubilized 5-HT1 sites retain high affinity for D-LSD binding site (IC50 = 75 nM). However, L-LSD also has a high affinity for the soluble binding site (IC50 of 200 nM). Thus while the membrane-bound binding site strongly differentiates between D- and L-LSD, both stereoisomers bind to the soluble binding site with relatively high affinity. Lovell and Freedman have suggested that the lone-pair electrons on the 3 nitrogen atoms in D-LSD are oriented downward from the plane of the molecule and form a tripod of electron donor pairs which interact with the 5-HT 1 binding site. This area of attachment of D-LSD would be expected to be much larger than the area of attachment of 5-HT to the binding site, and to overlap or encompass the 5- HT binding region. The lower affinity of L-LSD for the membrane binding site would be due to the fact that one or more of the lone-pair electrons is oriented above the plane of the molecule. The diethylamide group of L-LSD would also be oriented differently. It would therefore either be unavailable for interactions with the binding site or its orientation would be a steric hindrance to binding.