Hemin (trade name Panhematin) is a protoporphyrin IX containing a ferric iron ion (heme B) with a chloride ligand, which is is indicated for the amelioration of recurrent attacks of acute intermittent porphyria temporally related to the menstrual cycle in susceptible women. Manifestations such as pain, hypertension, tachycardia, abnormal mental status and mild to progressive neurologic signs may be controlled in selected patients with this disorder. the therapy for the acute porphyrias is not curative. Heme acts to limit the hepatic and/or marrow synthesis of porphyrin. This action is likely due to the inhibition of δ-aminolevulinic acid synthetase, the enzyme which limits the rate of the porphyrin/heme biosynthetic pathway. The exact mechanism by which hematin produces symptomatic improvement in patients with acute episodes of the hepatic porphyrias has not been elucidated.

Bromocriptine is an ergot derivative with potent dopamine receptor agonist activity, which activates post-synaptic dopamine receptors. Bromocriptine is indicated for the treatment of dysfunctions associated with hyperprolactinemia. Bromocriptine therapy is indicated in the treatment of acromegaly and in the treatment of the signs and symptoms of idiopathic or postencephalitic Parkinson’s disease. It is approved as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Some commonly reported adverse reactions include nausea, fatigue, dizziness, vomiting and headache. Bromocriptine may interact with dopamine antagonists, butyrophenones and certain other agents.

Levodopa (L-DOPA) was first isolated from seedlings of Vicia faba by Marcus Guggenheim in 1913. Levodopa, a dopamine precursor, is an effective and well-tolerated dopamine replacement agent used to treat Parkinson's disease. Oral levodopa has been widely used for over 40 years, often in combination with a dopa-decarboxylase inhibitor carbidopa, which reduces many treatment complications, extending its half-life and increasing levodopa availability to the brain. Entacapone, a catechol-O-methyltransferase inhibitor, can also be used to improve the bioavailability of levodopa, especially when used in conjunction with a carbidopa.

Amantadine hydrochloride has pharmacological actions as both an anti-Parkinson and an antiviral drug. The mechanism by which amantadine exerts its antiviral activity is not clearly understood. It appears to mainly prevent the release of infectious viral nucleic acid into the host cell by interfering with the function of the transmembrane domain of the viral M2 protein. In certain cases, amantadine is also known to prevent virus assembly during virus replication. It does not appear to interfere with the immunogenicity of inactivated influenza A virus vaccine. The mechanism of action of amantadine in the treatment of Parkinson's disease and drug-induced extrapyramidal reactions is not known. Data from earlier animal studies suggest that amantadine hydrochloride may have direct and indirect effects on dopamine neurons. More recent studies have demonstrated that amantadine is a weak, non-competitive NMDA receptor antagonist (K1 = 10µM). Although amantadine has not been shown to possess direct anticholinergic activity in animal studies, clinically, it exhibits anticholinergic-like side effects such as dry mouth, urinary retention, and constipation. Amantadine was approved by the FDA in 1966 as a prophylactic agent against Asian influenza, and eventually received approval for the treatment of influenza virus A in adults. In 1969, it was also discovered by accident to help reduce symptoms of Parkinson's disease, drug-induced extrapyramidal syndromes, and akathisia.

Trihexyphenidyl (Artane, Apo-Trihex, Parkin, Pacitane), also known as benzhexol and trihex has been in clinical usage for decades.It is an anticholinergic used in the symptomatic treatment of all etiologic groups of parkinsonism and drug induced extrapyramidal reactions (except tardive dyskinesia). Trihexyphenidyl possesses both anticholinergic and antihistaminic effects, although only the former has been established as therapeutically significant in the management of parkinsonism. Trihexyphenidyl is a selective M1 muscarinic acetylcholine receptor antagonist. It is able to discriminate between the M1 (cortical or neuronal) and the peripheral muscarinic subtypes (cardiac and glandular). Trihexyphenidyl partially blocks cholinergic activity in the CNS, which is responsible for the symptoms of Parkinson's disease. It is also thought to increase the availability of dopamine, a brain chemical that is critical in the initiation and smooth control of voluntary muscle movement. Trihexyphenidyl is indicated for the treatment of parkinson's disease and extrapyramidal reactions caused by drugs.

Apomorphine (brand names: Apokyn, Ixense, Spontane, Uprima) is indicated for the acute, intermittent treatment of hypomobility, “off” episodes (“end-of-dose wearing off” and unpredictable “on/off” episodes) in patients with advanced Parkinson’s disease. Apomorphine has been studied as an adjunct to other medications. It is a non-ergoline dopamine agonist with high in vitro binding affinity for the dopamine D4 receptor, and moderate affinity for the dopamine D2, D3, and D5, and adrenergic α1D, α2B, α2C receptors. The precise mechanism of action as a treatment for Parkinson’s disease is unknown, although it is believed to be due to stimulation of post-synaptic dopamine D2-type receptors within the caudate-putamen in the brain.

Apocynin, also known as acetovanillone, is a natural organic compound related to vanillin. It has been isolated from a variety of plant sources. Metabolites of apocynin are able to block the activity of NADPH oxidase, thus giving apocynin antioxidant and anti-inflammatory capabilities. Effects of apocynin on the concentration of reactive oxygen and nitrogen species in patients with asthma and chronic obstructive pulmonary disease were investigated in phase I clinical trials. In preclinical models, it was found that apocynin provides neuroprotective effects in models of stroke and Parkinson's disease.

Vipadenant (V2006) is a small molecule, adenosine A2A receptor antagonist that was being investigated in Parkinson's disease. Due to safety concerns development ceased in 2010 and the rights were regained from Biogen Idec in 2011 with no further investment made. In October 2014, RedoxTherapies licensed Vipadenant as it has the potential to disrupt an immunosuppressive mechanism of tumour protection, generating improved efficacy for immunotherapies of certain cancers when used in combination with other drugs.

Traxoprodil (CP-101,606) is a potent, selective N-Methyl-D-aspartate (NMDA) receptor (NR2B subunit) antagonist under development by Pfizer for its potential as a neuroprotectant in head injury and neurodegenerative disease. It is in phase II trials in the US and in phase I in Japan for the potential treatment of head injury, such as, Depressive Disorder, Major and Parkinson's Disease. CP-101,606 does not protect against glutamate-induced neurotoxicity in cultured cerebellar neurons, up to a dose of 10 uM. These results are consistent with CP-101,606 being a potent NMDA antagonist, selective for the type of NMDA receptor associated with the hippocampus. Some further investigation revealed that CP-101,606 was associated with a dose-related dissociation and amnesia. These results support the hypothesis that glutamate antagonists may be useful antidyskinetic agents. However, future studies will have to determine if the benefits of dyskinesia suppression can be achieved without adverse cognitive effects.

(-)-3-(3-hydroxyphenyl)-N-n-propylpiperidine ((-)-3-PPP, also known as preclamol) has a dual action towards to dopamine D2 autoreceptor: it activates it and also acts concomitantly as an antagonist at postsynaptic DA receptors. It was shown, that (-)-3PPP/preclamol was a safe drug for study in the treatment of schizophrenia and may have antipsychotic efficacy. Besides, the motor effects of the drug were evaluated in nine patients with Parkinson's disease using a double-blind, placebo-controlled design. However, the small number of patients manifesting a clinically significant response and the frequently inconsistent effects could indicate that this class of agents may have relatively limited clinical utility.