BMY-7378 is a multi-targeted inhibitor of α2C-adrenoceptor and α1D-adrenoceptor with pKi of 6.54 and 8.2, respectively, and acts as a mixed agonist and antagonist for 5-HT1A receptor with pKi of 8.3. BMY-7378 was at the preclinical stage of development for the treatment of anxiety disorders, but later was discontinued.

LY-165163 is a partial agonist of serotonin receptors 5-HT1A and 5-HT1D. It exhibits marked activity at both pre- and postsynaptic dopaminergic D2 (D3 and D1) receptors. LY-165163 caused a significant and dose-dependent hypothermia in rats. As a 5-HT1D receptor agonist, LY-165163 was proposed for the ocular pain treatment.

Selective, potent, orally bioavailable full 5-HT1A antagonist. S-(+)-enantiomer of (±)-LY426965 is more active in comparison with its opposite enantiomer (R)-(-)-LY 426965. LY426965 completely reversed the effects of nicotine withdrawal on the auditory startle reflex in rats. In microdialysis experiments, LY426965, when administered with fluoxetine, significantly increased extracellular levels of serotonin above those achievable with fluoxetine alone. In electrophysiological studies, the administration of LY426965 both blocked and reversed the effects of fluoxetine on 5-HT neuronal activity. Preclinical results indicate that LY426965 may have clinical use as a pharmacotherapy for smoking cessation and depression and related disorders.

WAY-100635 is an achiral phenylpiperazine derivative that originally discovered as an antagotist of 5-HT1A receptor. Later WAY-100635 was described as a potent dopamine D4 receptor agonist. WAY-100635 was in preclinical studies for the treatment of Diabetes mellitus, Anxiety and Cognition disorders, howevere the development was discontinued. Isotope labeled WAY-100635 could be used for the study of central 5-HT 1A receptors with potential for application to the study of neuropsychiatric disorders and to the human pharmacology of psychoactive drugs.

Lysergol {LYZ; (7-methyl- 4,6,6a,7,8,9-hexahydro-indolo[4,3-fg]quinolin-9-yl)-methanol} has shown potential to enhance BA of berberine (poorly water soluble herbal anticancer agent). It is obtained from the seeds of Ipomoea muricata, I. turbinate and Calonyction muricata belonging to the family Convolvulaceae. Seeds are commonly known as ‘Kaladana’ in trade and are being used as a purgative in India and Pakistan. LYZ is an indole alkaloid present in the microfungi of Claviceps purpurea as well. It is one of the minor constituents of the ancient Mexican hallucinogenic drug Ololiuqui, which is obtained from Rivea corymbosa seeds. LYZ has been used by the 17th century midwives to induce labour and stop postpartum bleeding because of its ability to induce uterine contractions. It may also cause ergot poisoning, diarrhea, hallucinations, delirium, seizures, burning sensations, and gangrene in the limbs. However, it is not being used presently in the clinic.

Yohimbine is a plant alkaloid with alpha-2-adrenergic blocking activity. Yohimbine has been used as a mydriatic and in the treatment of impotence. The exact mechanism for its use in impotence has not been fully elucidated. Yohimbine exerts antagonist actions at halpha(2A)-AR, h5-HT(1B), h5-HT(1D), and hD(2) sites, partial agonist actions at h5-HT(1A) sites. Yohimbine-mediated norepinephrine release at the level of the corporeal tissues may also be involved. In addition, beneficial effects may involve other neurotransmitters such as dopamine and serotonin and cholinergic receptors. Yohimbine has a mild anti-diuretic action, probably via stimulation of hypothalmic center and release of posterior pituitary hormone. Reportedly yohimbine exerts no significant influence on cardiac stimulation and other effects mediated by (beta)-adrenergic receptors. Its effect on blood pressure, if any, would be to lower it; however, no adequate studies are at hand to quantitate this effect in terms of Yohimbine dosage. Side effect of Yohimbine include anxiety, tremor, palpitations, diarrhea, and supine hypertension.

Penbutolol is a new beta-adrenergic blocking drug approved for the treatment of hypertension. It is a noncardioselective beta-blocker and has intrinsic sympathomimetic activity. Penbutolol is marketed under the trade names Levatol, Levatolol, Lobeta, Paginol, Hostabloc, Betapressin. Penbutolol acts on the β1 adrenergic receptors in both the heart and the kidney. When β1 receptors are activated by catecholamines, they stimulate a coupled G protein that leads to the conversion of adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP). The increase in cAMP leads to activation of protein kinase A (PKA), which alters the movement of calcium ions in heart muscle and increases the heart rate. Penbutolol blocks the catecholamine activation of β1 adrenergic receptors and decreases heart rate, which lowers blood pressure. Levatol (Penbutolol) is indicated in the treatment of mild to moderate arterial hypertension. It may be used alone or in combination with other antihypertensive agents, especially thiazide-type diuretics.

LP-20 (1-[2-(4-Methoxyphenyl)phenyl]piperazine) is a potent serotonin 5-HT7 receptor antagonist with a low binding affinity for the 5-HT1A and adrenergic 1 receptor. In animal models LP-20 was investigated as a potential positron emission tomography (PET) radiotracer, due to high synthetic availability of 11C radiolabeled compound. Although [11C] LP-20 exhibited in vitro binding with 5-HT7, moderate brain uptake and relatively stable metabolism in the brain, in vivo evaluation showed limited specificity of [11C] LP-20 for 5-HT7.