A Fresh Approach to the Psychopharmacology of Libido

A brief for physicians regarding low libido and sexual desire especially in long term relationships
By Dr. George Dodd

As the primary health and social needs of most adults in developed countries are now being met, there is increasing emphasis on secondary conditions which affect the quality of life. The effects of ageing has prompted an increasing interest is cosmetic treatments and surgery for both men and women.

In a similar fashion, there are now high expectations of sexual fulfilment in long-term relationships. The ‘Viagra Effect’ transformed expectations for men and the current family of drugs for erectile dysfunction ensure that men, especially older men, have the physical basis for sexual expression. Largely because of severe side effects, similar drugs for women have failed to make it to the market.

The intense research which followed on the discovery of Viagra – a serendipitous discovery in a program on cardiovascular pharmacology – has focussed on the neglected area of desire in sexual behaviour. A progressive lack of sexual desire is found in both genders in long-term relationships and is thought to be especially prevalent in women. The condition of Female Sexual Desire Disorder (FSDD) is now an official minor psychiatric condition which is codified in the Diagnostic and Statistical Manual.

The Dopamine-Olfaction Relationship
It is well known that dopamine is one of the neurotransmitters involved in sexual arousal. Therefore, following the well known dopamine receptor approach to the development of anti-psychotic drugs, various pharmaceutical companies investigated the sexual desire potential of drugs which were known to increase dopamine levels in the limbic system of the central nervous system (CNS).  Positive effects were found but unfortunately, the severity of the side effects resulted in the programs being abandoned.

Encouraged by the positive results found for FSSD with drugs that were aimed at modulating dopamine levels, our research focussed on mood and desire in sexual relationships with the aim of discovering a non toxic approach to re-kindling lost desire. Side-effects result from drugs being present at high levels in the blood and interacting with multiple receptors instead of being able to target the specific receptors in the CNS.

It was apparent to us that classical CNS pharmacology had neglected the opportunities provided by the distinctive anatomy and molecular pharmacology of the olfactory system.  Our sniffer cells, the primary olfactory neurones, are fully functional CNS neurones which happen to have their dendrites (which can be regarded as an open-ended synapse) and cell body in the olfactory epithelium which lies outside of the brain cavity in the region of the cribriform plate. The axons from these specialized and functional CNS neurones pass through the cribriform plate and form complex synaptic connections with mitral cells in the olfactory bulb. The olfactory tract continues into the limbic system, the key site of action of important CNS drugs, and this collection of specific brain centres process the mood and memory effects which are prominent features of olfactory stimulation. The olfactory tract is known to be rich in dopamine receptors.

Since the early 1970s, we have been pioneers in olfactory biochemistry and our research group was one of the first to establish the key biochemical steps in olfactory transduction in the primary olfactory neurones. It is now thought that many olfactory receptor proteins have the classical trans-membrane protein profile of many CNS neurotransmitter receptors, including receptors for dopamine.

DMOs – Dopamine Mimetic Odorants
Dopamine does not have an odour and is therefore not an agonist (odorant) for olfactory neurones. But just as it is now apparent that many of the serendipitously discovered naturally-occurring CNS drugs are mimetics of endogenous agonists (neurotransmitters or neuro-modulators), we invented, by analogy, the notion of dopamine mimetic odorant (DMOs).  The structure of some of the DMOs were presented in an abstract and presented at the International Society for the Study of Women’s Sexual Health in Prague, 2006.

The final aroma formulation for Scentuelle, a non drug solution for low libido, is an extraordinarily complex medical perfume and exhibit marked synergistic effects with other odorants. It is likely that this form of odorant polypharmacy addresses multiple neurotransmitter systems although it is addressed primarily at dopamine receptors.

The most striking feature exemplified by Scentuelle, is a lack of side effects. We cite this as an example of molecular engineering in pharmacology. The explanation for the non-existence of side-effects is this that the agonists are volatile molecules (odorants) which diffuse to the receptor proteins located on the external surface of the cilia of the dendrites of the primary olfactory neurones, where they bind reversibly to the binding sites. The binding initiates an enzyme-mediated cascade (involving cAMP – a key second messenger in the sensing of odorants by the primary olfactory neurons – and related molecules) which leads to depolarization of the olfactory dendrites. The odorants then de-adsorb from the receptor sites and are exhaled into the surrounding atmosphere.

The crucial point is that in contrast to conventional drugs, which diffuse from plasma to the binding sites and which occur at high levels in plasma, no amount of odorant sufficient to activate any known receptor is found in plasma.

Scentuelle is readily accepted by patients and is an easy to use transparent patch that is worn on the wrist and smelled frequently throughout the day. The efficacy has been established in user trials which are available upon request.

Dr. George Dodd is a leading researcher in the science of smell and the Director of Product Research and Development for The Sense of Smell Lab.

www.scentuellepatch.com
Email: george@naturalperfumes.com