Psychiatric disorders, treatment receptors

A recent patent application from Roche [352] described a 2-amino-benzothiazole series. Roche claimed that compound (605) exhibited an IC50 value of 0.73 uM at CBi, and showed in excess of 10-fold selectivity over the CB2 receptor. The compounds were described as being of potential use in the treatment of a range of diseases, including CNS and psychiatric disorders, type-2 diabetes, gastrointestinal diseases, cardiovascular disorders, infertility disorders, inflammation, cancer, atherosclerosis, cerebral vascular incidents and cranial trauma. 

The early suggestion by Fozard [54] that 5-HT3 receptor antagonists may be useful in the treatment of migraine has yet to be established, although MDL 72222 appeared to be effective in limited clinical trials [94, 95]. There are exciting prospects for other clinical applications of 5-HT3 antagonists in psychiatric disorders which have been predicted from behavioural studies in rodents and primates, and several clinical trials are underway in psychiatric patients. 

Dopamine activity can be enhanced in one of four main ways. Medications can stimulate dopaminergic nerve cells to release dopamine into the synapse. This is the way that stimulants such as methylphenidate (Ritalin), dextroamphetamine (Dexe-drine), and dextroamphetamine/amphetamine (Adderall) work. In addition, certain drugs of abuse, notably cocaine and methamphetamine, act in part in this way. Providing more of the raw material that nerve cells use to manufacture dopamine can also increase dopamine activity. This is the approach that neurologists use when they prescribe L-DOPA (Sinemet) to patients with Parkinson s disease. Nerve cells convert L-DOPA into dopamine. L-DOPA otherwise has little place in the treatment of psychiatric disorders. Dopamine activity can also be increased by medications that directly stimulate dopamine receptors. Bromocriptine, another medication used to... 

Information processing in the human brain via neuro-chemically defined neuronal systems is complex. Therefore, it remains a challenge to conceptualize psychiatric disorders and their treatment in a reductionistic framework of chemical neuroanatomy. We can nonetheless broadly state that the anatomic organization of neurotransmitter systems determines their behavioral affiliation, and that receptors modulate the electrical or biochemical properties of neurons, with direct relevance to the mechanism of action of psychotropic drugs. Future research will provide more detailed information on the subtypes of neurons and specific neurotransmitters systems that are abnormal in psychiatric disorders, and provide a more rational approach to the development of new treatment interventions. 

Whitworth P, Kendall DA Effects of lithium on inositol phospholipid hydrolysis and inhibition of dopamine D, receptor-mediated cyclic AMP formation by carbachol in rat brain slices. J Neurochem 53 536-541, 1989 Whybrow PC The therapeutic use of triiodothyronine and high dose thyroxine in psychiatric disorder. Acta Med Austriaca 21 44-47, 1994 Whybrow PC Update on thyroid axis approaches to treatment of rapid cycling bipolar disorder. Paper presented at the annual meeting of the New Clinical Drug Evaluations Unit (NCDEU), Boca Raton, EL, May 30, 1996... 

Dopamine is a major neurotransmitter which acts on multiple receptors. It can activate both a and 3 adrenoceptors in addition to acting on specific dopamine receptors. These are widely distributed throughout the CNS and are also present in the renal tubules and renal and mesentric blood vessels, and many dopaminergic drugs are used in the treatment of Parkinson s disease, psychiatric disorders, as antiemetics, and for renal protection. Neuroleptic drugs, such as haloperidol and droperidol, are dopamine receptor antagonists. 

Many earlier reports considered extrapyramidal side effects unavoidable when treating patients with neuroleptics. There appeared to he a parallel between antipsychotic action and the incidence of unwanted neurological effects. However, the development of newer neuroleptics has changed this view. Drugs like clozapine have a high antipsychotic potency and yet produce few neurological problems. It has therefore been proposed that the DA receptors involved in the beneficial actions of neuroleptics in the treatment of psychiatric disorders are situated in mesolimbic areas, such as the nucleus accumbens, whereas the extrapyramidal effects are mediated by striatal receptors. 

Cell surface receptors are clearly of great importance in understanding the function of the nervous system, the endocrine system, the immune system, cell proliferation, and targets for infection. The major chronic diseases such as cancer, diabetes, heart disease, arthritis, autoimmune disease, necrologic and psychiatric disorders, and endocrine dysfunction involve interactions with cell surface receptors. Understanding the structure and function of surface receptors has grown into one of the great thrusts of pharmaceutical R D, pursued in the belief it will uncover as yet unknown approaches to treatment of diseases hitherto intractable. 

C raclopride and [ l]iodobenzamine are used to study Dj DA receptors "C cocaine studies DA transporters. Transporters are often targets for treatment of psychiatric disorders, including depression and substance abuse. 

HT2-type receptors have been a focus for investigations into its putative clinical importance for treatment of psychiatric disorders. h-HTg-type receptors have been implicated in several disorders like anxiety, depression and psychosis. As we are presently in the dark with respect to the mechanisms underlying the development of these disorders, future pharmacotherapy largely aims at alleviating symptoms. To that end various compounds, which have antagonistic properties on S-HTj-type receptors, are currently tested in clinical studies. 

The Barton-Zard reaction found its application in the synthesis of LY2059346, a positive allosteric modulator of the a-amino-3-hydroxyl-L-aspartate (AMPA) receptor as a potential treatment of neurological and psychiatric disorders. ... 

Anxiety and depression are psychiatric disorders that constitute a major health problem throughout world. While numerous marketed treatments exist for both disorders, there remains a continuing need for drugs with increased efficacy and/or reduced side-effect profiles [164,165]. CRF (1) receptor antagonists have been proposed as novel pharmacological treatments for depression, anxiety and stress disorders [164-166]. 

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