Lerimazoline is a sympathomimetic drug that belongs to the imidazoline class of compounds, and is used as a nasal decongestant. Lerimazoline displayed high affinity for the 5-HT1A receptor and for the 5-HT1D receptor. Binding affinity estimates for α1-adrenoceptor, 5-HT2A, and D2 receptors were more than ten times lower. The mechanism of vasoconstrictor action of lerimazoline encompasses both, the activation of 5-HT2A, and to a lesser degree α1 -adrenergic receptors. These results also suggest that lerimazoline is an “atypical” decongestant. It inhibits secretion of nasal mucus. Lerimazoline causes hypertension.

FLESINOXAN, a phenylpiperazine derivative, is a selective agonist for 5-HT1A receptors. It is an antidepressant agent which clinical development was stopped.

Mazapertine (RWJ-37796) is an arylpiperazine antipsychotic with high affinity to dopamine D2 and D3, serotonin 5-HT1A and alpha 1A-adrenergic receptors. It was being studied in the treatment of schizophrenia.

Bifeprunox, code name DU-127,090 is an atypical antipsychotic agent, which combines minimal D2 receptor agonism with 5-HT receptor agonism. Bifeprunox was in phase III of clinical trials for the treatment of schizophrenia, Bipolar Depression and in phase I for Parkinson's disease, but these studies were discontinued because efficacy data did not support pursuing the existing development strategy of stabilization of non-acute patients with schizophrenia.

Pardoprunox is a partial D2/3 dopamine receptor agonist and full 5-HT1A serotonin receptor agonist. Partial D(2/3) dopamine (DA) receptor agonists provide a novel approach to the treatment of the motor symptoms of Parkinson's disease that may avoid common dopaminergic side effects, including dyskinesia and psychosis. Pardoprunox passed phase III clinical trial for the treatment of Parkinson's disease.

Caprindolol, also known as SDZ 21009, is a beta-adrenoceptor blocker with affinity for serotonin (5-HT1A and 5-HT1B receptors.

Osemozotan (also known as MKC-242) was developed as a selective 5-HT1A receptor agonist. Experiments on animal have shown that osemozotan improved most abnormal behaviors such as isolation rearing. Osemozotan was being investigated for the treatment of pain, aggressive behavior, anxiety, depression, obsessive-compulsive disorder, and drug dependence with methamphetamine and cocaine. However, all these studies were suspended. In the USA osemozotan participated in phase II clinical trial for the insomnia patients, however, the study was terminated because of the license agreement.

Spiroxatrine is a drug which acts as a selective antagonist at both the 5-HT1A receptor and the α2 adrenergic receptor. Spiroxatrine was identified as a moderately potent but non-selective agonist at the human nociceptin/orphanin FQ receptor, ORL1